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Priming cancer cells for drug resistance: role of the fibroblast niche

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  • Published:
Frontiers in Biology

Abstract

Conventional and targeted chemotherapies remain integral strategies to treat solid tumors. Despite the large number of anti-cancer drugs available, chemotherapy does not completely eradicate disease. Disease recurrence and the growth of drug resistant tumors remain significant problems in anti-cancer treatment. To develop more effective treatment strategies, it is important to understand the underlying cellular and molecular mechanisms of drug resistance. It is generally accepted that cancer cells do not function alone, but evolve through interactions with the surrounding tumor microenvironment. As key cellular components of the tumor microenvironment, fibroblasts regulate the growth and progression of many solid tumors. Emerging studies demonstrate that fibroblasts secrete a multitude of factors that enable cancer cells to become drug resistant. This review will explore how fibroblast secretion of soluble factors act on cancer cells to enhance cancer cell survival and cancer stem cell renewal, contributing to the development of drug resistant cancer.

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References

  • Ablett M P O B C, Sims A H, Farnie G, Clarke R B (2013). A differential role for CXCR4 in the regulation of normal versus malignant breast stem cell activity. OncotargetEpub.

    Google Scholar 

  • Adams D J, Knick V C (1995). P-glycoprotein mediated resistance to 5′-nor-anhydro-vinblastine (Navelbine). Invest New Drugs, 13(1): 13–21

    PubMed  CAS  Google Scholar 

  • Addadi Y, Moskovits N, Granot D, Lozano G, Carmi Y, Apte R N, Neeman M, Oren M (2010). p53 status in stromal fibroblasts modulates tumor growth in an SDF1-dependent manner. Cancer Res, 70(23): 9650–9658

    PubMed  CAS  PubMed Central  Google Scholar 

  • Aguirre-Ghiso J A, Ossowski L, Rosenbaum S K (2004). Green fluorescent protein tagging of extracellular signal-regulated kinase and p38 pathways reveals novel dynamics of pathway activation during primary and metastatic growth. Cancer Res, 64(20): 7336–7345

    PubMed  CAS  Google Scholar 

  • Ahn S, Cho J, Sung J, Lee J E, Nam S J, Kim K M, Cho E Y (2012). The prognostic significance of tumor-associated stroma in invasive breast carcinoma. Tumour Biol, 33(5): 1573–1580

    PubMed  Google Scholar 

  • Aishima S, Taguchi K, Terashi T, Matsuura S, Shimada M, and Tsuneyoshi M (2003). Tenascin expression at the invasive front is associated with poor prognosis in intrahepatic cholangiocarcinoma. Modern pathology: an official journal of the United States and Canadian Academy of Pathology, Inc 16(10), 1019–1027

    Google Scholar 

  • Allavena P, Germano G, Marchesi F, Mantovani A (2011). Chemokines in cancer related inflammation. Exp Cell Res, 317(5): 664–673

    PubMed  CAS  Google Scholar 

  • Allinen M, Beroukhim R, Cai L, Brennan C, Lahti-Domenici J, Huang H, Porter D, Hu M, Chin L, Richardson A, Schnitt S, Sellers W R, Polyak K (2004). Molecular characterization of the tumor microenvironment in breast cancer. Cancer Cell, 6(1): 17–32

    PubMed  CAS  Google Scholar 

  • Amar S, Roy V, Perez E A (2009). Treatment of metastatic breast cancer: looking towards the future. Breast Cancer Res Treat, 114(3): 413–422

    PubMed  Google Scholar 

  • Anastas J N, Moon R T (2013). WNT signalling pathways as therapeutic targets in cancer. Nat Rev Cancer, 13(1): 11–26

    PubMed  CAS  Google Scholar 

  • Astsaturov I, Ratushny V, Sukhanova A, Einarson M B, Bagnyukova T, Zhou Y, Devarajan K, Silverman J S, Tikhmyanova N, Skobeleva N, Pecherskaya A, Nasto R E, Sharma C, Jablonski S A, Serebriiskii I G, Weiner L M, Golemis E A (2010). Synthetic lethal screen of an EGFR-centered network to improve targeted therapies. Sci Signal, 3(140): ra67

    PubMed  PubMed Central  Google Scholar 

  • Ayala G, Tuxhorn J A, Wheeler T M, Frolov A, Scardino P T, Ohori M, Wheeler M, Spitler J, Rowley D R (2003). Reactive stroma as a predictor of biochemical-free recurrence in prostate cancer. Clin Cancer Res, 9(13): 4792–4801

    PubMed  CAS  Google Scholar 

  • Balkwill F R (2012). The chemokine system and cancer. J Pathol, 226(2): 148–157

    PubMed  CAS  Google Scholar 

  • Balkwill F R, Mantovani A (2012). Cancer-related inflammation: common themes and therapeutic opportunities. Semin Cancer Biol, 22(1): 33–40

    PubMed  CAS  Google Scholar 

  • Bao L, Haque A, Jackson K, Hazari S, Moroz K, Jetly R, Dash S (2011). Increased expression of P-glycoprotein is associated with doxorubicin chemoresistance in the metastatic 4T1 breast cancer model. Am J Pathol, 178(2): 838–852

    PubMed  CAS  PubMed Central  Google Scholar 

  • Bao S, Ouyang G, Bai X, Huang Z, Ma C, Liu M, Shao R, Anderson R M, Rich J N, Wang X F (2004). Periostin potently promotes metastatic growth of colon cancer by augmenting cell survival via the Akt/PKB pathway. Cancer Cell, 5(4): 329–339

    PubMed  CAS  Google Scholar 

  • Baril P, Gangeswaran R, Mahon P C, Caulee K, Kocher H M, Harada T, Zhu M, Kalthoff H, Crnogorac-Jurcevic T, and Lemoine N R (2007). Periostin promotes invasiveness and resistance of pancreatic cancer cells to hypoxia-induced cell death: role of the beta4 integrin and the PI3k pathway. Oncogene 26(14), 2082–2094

    PubMed  CAS  Google Scholar 

  • Bielen H, Houart C (2014). The Wnt Cries Many: Wnt regulation of neurogenesis through tissue patterning, proliferation and asymmetric cell division. Dev Neurobiol, doi: 10.1002/dneu.22168

    Google Scholar 

  • Binaschi M, Supino R, Gambetta R A, Giaccone G, Prosperi E, Capranico G, Cataldo I, Zunino F (1995). MRP gene overexpression in a human doxorubicin-resistant SCLC cell line: alterations in cellular pharmacokinetics and in pattern of cross-resistance. Int J Cancer, 62(1): 84–89

    PubMed  CAS  Google Scholar 

  • Brellier F, Chiquet-Ehrismann R (2012). How do tenascins influence the birth and life of a malignant cell? J Cell Mol Med, 16(1): 32–40

    PubMed  CAS  Google Scholar 

  • Brewster A M, Hortobagyi G N, Broglio K R, Kau S W, Santa-Maria C A, Arun B, Buzdar A U, Booser D J, Valero V, Bondy M, Esteva F J (2008). Residual risk of breast cancer recurrence 5 years after adjuvant therapy. J Natl Cancer Inst, 100(16): 1179–1183

    PubMed  Google Scholar 

  • Brunner A, Mayerl C, Tzankov A, Verdorfer I, Tschörner I, Rogatsch H, Mikuz G (2004). Prognostic significance of tenascin-C expression in superficial and invasive bladder cancer. J Clin Pathol, 57(9): 927–931

    PubMed  CAS  PubMed Central  Google Scholar 

  • Buck M B, Pfizenmaier K, Knabbe C (2004). Antiestrogens induce growth inhibition by sequential activation of p38 mitogen-activated protein kinase and transforming growth factor-beta pathways in human breast cancer cells. Mol Endocrinol, 18(7): 1643–1657

    PubMed  CAS  Google Scholar 

  • Burger J A, and Kipps T J (2006). CXCR4: a key receptor in the crosstalk between tumor cells and their microenvironment. Blood, 107(5): 1761–1767

    PubMed  CAS  Google Scholar 

  • Busam K J (2011). Desmoplastic melanoma. Clin Lab Med, 31(2): 321–330

    PubMed  Google Scholar 

  • Buyukbayram H, Arslan A (2002). Value of tenascin-C content and association with clinicopathological parameters in uterine cervical lesions. Int J Cancer, 100(6): 719–722

    PubMed  CAS  Google Scholar 

  • Camps J L, Chang S M, Hsu T C, Freeman M R, Hong S J, Zhau H E, von Eschenbach A C, Chung L W (1990). Fibroblast-mediated acceleration of human epithelial tumor growth in vivo. Proc Natl Acad Sci USA, 87(1): 75–79

    PubMed  CAS  PubMed Central  Google Scholar 

  • Cecchi F, Rabe D C, Bottaro D P (2010). Targeting the HGF/Met signalling pathway in cancer. Eur J Cancer, 46(7): 1260–1270

    PubMed  CAS  PubMed Central  Google Scholar 

  • Chao C, Carmical J R, Ives K L, Wood T G, Aronson J F, Gomez G A, Djukom C D, Hellmich M R (2012). CD133 + colon cancer cells are more interactive with the tumor microenvironment than CD133-cells. Lab Invest, 92(3): 420–436

    PubMed  CAS  PubMed Central  Google Scholar 

  • Chen J T, Huang C Y, Chiang Y Y, Chen W H, Chiou S H, Chen C Y, Chow K C (2008). HGF increases cisplatin resistance via downregulation of AIF in lung cancer cells. Am J Respir Cell Mol Biol, 38(5): 559–565

    PubMed  CAS  Google Scholar 

  • Chen S S, Lee L (1984). Prognostic significance of morphology of tumor and retroperitoneal lymph nodes in epithelial carcinoma of the ovary. II. Correlation with survival. Gynecol Oncol, 18(1): 94–99

    PubMed  CAS  Google Scholar 

  • Choi K U, Yun J S, Lee I H, Heo S C, Shin S H, Jeon E S, Choi Y J, Suh D S, Yoon M S, Kim J H (2011). Lysophosphatidic acid-induced expression of periostin in stromal cells: Prognoistic relevance of periostin expression in epithelial ovarian cancer. Int J Cancer, 128(2): 332–342

    PubMed  CAS  Google Scholar 

  • Cohen M, Marchand-Adam S, Lecon-Malas V, Marchal-Somme J, Boutten A, Durand G, Crestani B, Dehoux M (2006). HGF synthesis in human lung fibroblasts is regulated by oncostatin M. Am J Physiol Lung Cell Mol Physiol, 290(6): L1097–L1103

    PubMed  CAS  Google Scholar 

  • Cohen S J, Alpaugh R K, Palazzo I, Meropol N J, Rogatko A, Xu Z, Hoffman J P, Weiner L M, Cheng J D (2008). Fibroblast activation protein and its relationship to clinical outcome in pancreatic adenocarcinoma. Pancreas, 37(2): 154–158

    PubMed  CAS  Google Scholar 

  • Conklin M W, Keely P J (2012). Why the stroma matters in breast cancer: insights into breast cancer patient outcomes through the examination of stromal biomarkers. Cell Adhes Migr, 6(3): 249–260

    Google Scholar 

  • Conti I, Rollins B J (2004). CCL2 (monocyte chemoattractant protein-1) and cancer. Semin Cancer Biol, 14(3): 149–154

    PubMed  CAS  Google Scholar 

  • Dačević M, Isaković A, Podolski-Renić A, Isaković A M, Stanković T, Milošević Z, Rakić L, Ruždijić S, Pešić M (2013). Purine nucleoside analog-sulfinosine modulates diverse mechanisms of cancer progression in multi-drug resistant cancer cell lines. PLoS ONE, 8(1): e54044

    PubMed  PubMed Central  Google Scholar 

  • Daly A J, McIlreavey L, Irwin C R (2008). Regulation of HGF and SDF-1 expression by oral fibroblasts-implications for invasion of oral cancer. Oral Oncol, 44(7): 646–651

    PubMed  CAS  Google Scholar 

  • de Boer R A, van Veldhuisen D J, Gansevoort R T, Muller Kobold A C, van Gilst W H, Hillege H L, Bakker S J, van der Harst P (2012). The fibrosis marker galectin-3 and outcome in the general population. J Intern Med, 272(1): 55–64

    PubMed  Google Scholar 

  • de Boussac H, Orbán T I, Várady G, Tihanyi B, Bacquet C, Brózik A, Váradi A, Sarkadi B, Arányi T (2012). Stimulus-induced expression of the ABCG2 multidrug transporter in HepG2 hepatocarcinoma model cells involves the ERK1/2 cascade and alternative promoters. Biochem Biophys Res Commun, 426(2): 172–176

    PubMed  Google Scholar 

  • De Wever O, Nguyen Q D, Van Hoorde L, Bracke M, Bruyneel E, Gespach C, Mareel M (2004). Tenascin-C and SF/HGF produced by myofibroblasts in vitro provide convergent pro-invasive signals to human colon cancer cells through RhoA and Rac. FASEB J, 18(9): 1016–1018

    PubMed  Google Scholar 

  • Dean M (2009). ABC transporters, drug resistance, and cancer stem cells. J Mammary Gland Biol Neoplasia, 14(1): 3–9

    PubMed  Google Scholar 

  • Deng B, Huang W, Tan Q Y, Fan X Q, Jiang Y G, Liu L, Zhong Y Y, Liang Y G, Wang R W (2011). Breast cancer anti-estrogen resistance protein 1 (BCAR1/p130cas) in pulmonary disease tissue and serum. Mol Diagn Ther, 15(1): 31–40

    PubMed  CAS  Google Scholar 

  • DeVita V T Jr, Chu E (2008). A history of cancer chemotherapy. Cancer Res, 68(21): 8643–8653

    PubMed  CAS  Google Scholar 

  • Diah S K, Smitherman P K, Aldridge J, Volk E L, Schneider E, Townsend A J, Morrow C S (2001). Resistance to mitoxantrone in multidrug-resistant MCF7 breast cancer cells: evaluation of mitoxantrone transport and the role of multidrug resistance protein family proteins. Cancer Res, 61(14): 5461–5467

    PubMed  CAS  Google Scholar 

  • Diaz L A, Jr., Williams R T, Wu J, Kinde I, Hecht J R, Berlin J, Allen B, Bozic I, Reiter J G, Nowak M A, Kinzler K W, Oliner K S, and Vogelstein B (2012). The molecular evolution of acquired resistance to targeted EGFR blockade in colorectal cancers. Nature 486(7404), 537–540

    PubMed  PubMed Central  Google Scholar 

  • Domanska U M, Timmer-Bosscha H, Nagengast W B, Oude Munnink T H, Kruizinga R C, Ananias H J, Kliphuis NM, Huls G, De Vries E G, de Jong I J, Walenkamp A M (2012). CXCR4 inhibition with AMD3100 sensitizes prostate cancer to docetaxel chemotherapy. Neoplasia, 14(8): 709–718

    PubMed  CAS  PubMed Central  Google Scholar 

  • Dubrovska A, Elliott J, Salamone R J, Telegeev G D, Stakhovsky A E, Schepotin I B, Yan F, Wang Y, Bouchez L C, Kularatne S A, Watson J, Trussell C, Reddy V A, Cho C Y, Schultz P G (2012). CXCR4 expression in prostate cancer progenitor cells. PLoS ONE, 7(2): e31226

    PubMed  CAS  PubMed Central  Google Scholar 

  • Earp H S, Dawson T L, Li X, Yu H (1995). Heterodimerization and functional interaction between EGF receptor family members: a new signaling paradigm with implications for breast cancer research. Breast Cancer Res Treat, 35(1): 115–132

    PubMed  CAS  Google Scholar 

  • Emoto K, Yamada Y, Sawada H, Fujimoto H, Ueno M, Takayama T, Kamada K, Naito A, Hirao S, and Nakajima Y (2001). Annexin II overexpression correlates with stromal tenascin-C overexpression: a prognostic marker in colorectal carcinoma. Cancer, 92(6): 1419–1426

    PubMed  CAS  Google Scholar 

  • Erbas B, Provenzano E, Armes J, Gertig D (2006). The natural history of ductal carcinoma in situ of the breast: a review. Breast Cancer Res Treat, 97(2): 135–144

    PubMed  Google Scholar 

  • Eyman D, Damodarasamy M, Plymate S R, Reed M J (2009). CCL5 secreted by senescent aged fibroblasts induces proliferation of prostate epithelial cells and expression of genes that modulate angiogenesis. J Cell Physiol, 220(2): 376–381

    PubMed  CAS  PubMed Central  Google Scholar 

  • Fang W B, Jokar I, Zou A, Lambert D, Dendukuri P, Cheng N (2012). CCL2/CCR2 chemokine signaling coordinates survival and motility of breast cancer cells through Smad3 protein- and p42/44 mitogenactivated protein kinase (MAPK)-dependent mechanisms. J Biol Chem, 287(43): 36593–36608

    PubMed  CAS  PubMed Central  Google Scholar 

  • Feig C, Jones J O, Kraman M, Wells R J, Deonarine A, Chan D S, Connell C M, Roberts E W, Zhao Q, Caballero O L, Teichmann S A, Janowitz T, Jodrell D I, Tuveson D A, Fearon D T (2013). Targeting CXCL12 from FAP-expressing carcinoma-associated fibroblasts synergizes with anti-PD-L1 immunotherapy in pancreatic cancer. Proc Natl Acad Sci USA, 110(50): 20212–20217

    PubMed  CAS  PubMed Central  Google Scholar 

  • Flaherty K T, Puzanov I, Kim K B, Ribas A, McArthur G A, Sosman J A, O’Dwyer P J, Lee R J, Grippo J F, Nolop K, Chapman P B (2010). Inhibition of mutated, activated BRAF in metastatic melanoma. N Engl J Med, 363(9): 809–819

    PubMed  CAS  PubMed Central  Google Scholar 

  • Fleming J M, Miller T C, Kidacki M, Ginsburg E, Stuelten C H, Stewart D A, Troester M A, Vonderhaar B K (2012). Paracrine interactions between primary human macrophages and human fibroblasts enhance murine mammary gland humanization in vivo. Breast Cancer Res, 14(3): R97

    PubMed  CAS  PubMed Central  Google Scholar 

  • Foley J, Nickerson N K, Nam S, Allen K T, Gilmore J L, Nephew K P, Riese D J 2nd (2010). EGFR signaling in breast cancer: bad to the bone. Semin Cell Dev Biol, 21(9): 951–960

    PubMed  CAS  PubMed Central  Google Scholar 

  • Fujimoto H, Sangai T, Ishii G, Ikehara A, Nagashima T, Miyazaki M, Ochiai A (2009). Stromal MCP-1 in mammary tumors induces tumor-associated macrophage infiltration and contributes to tumor progression. Int J Cancer, 125(6): 1276–1284

    PubMed  CAS  Google Scholar 

  • Fukunaga-Kalabis M, Martinez G, Nguyen T K, Kim D, Santiago-Walker A, Roesch A, and Herlyn M (2010). Tenascin-C promotes melanoma progression by maintaining the ABCB5-positive side population. Oncogene, 29(46): 6115–6124

    PubMed  CAS  PubMed Central  Google Scholar 

  • Gao C F, Vande Woude G F (2005). HGF/SF-Met signaling in tumor progression. Cell Res, 15(1): 49–51

    PubMed  Google Scholar 

  • Gillan L, Matei D, Fishman D A, Gerbin C S, Karlan B Y, Chang D D (2002). Periostin secreted by epithelial ovarian carcinoma is a ligand for alpha(V)beta(3) and alpha(V)beta(5) integrins and promotes cell motility. Cancer Res, 62(18): 5358–5364

    PubMed  CAS  Google Scholar 

  • Goldberg R M (2006). Intensive surveillance after stage II or III colorectal cancer: is it worth it? J Clin Oncol, 24(3): 330–331

    PubMed  Google Scholar 

  • Gong X G, Lv Y F, Li X Q, Xu F G, Ma Q Y (2010). Gemcitabine resistance induced by interaction between alternatively spliced segment of tenascin-C and annexin A2 in pancreatic cancer cells. Biol Pharm Bull, 33(8): 1261–1267

    PubMed  CAS  Google Scholar 

  • Guirouilh J, Castroviejo M, Balabaud C, Desmouliere A, Rosenbaum J (2000). Hepatocarcinoma cells stimulate hepatocyte growth factor secretion in human liver myofibroblasts. Int J Oncol, 17(4): 777–781

    PubMed  CAS  Google Scholar 

  • Gupta V, Bassi D E, Simons J D, Devarajan K, Al-Saleem T, Uzzo R G, Cukierman E (2011). Elevated expression of stromal palladin predicts poor clinical outcome in renal cell carcinoma. PLoS ONE, 6(6): e21494

    PubMed  CAS  PubMed Central  Google Scholar 

  • Hasebe T, Mukai K, Tsuda H, Ochiai A (2000). New prognostic histological parameter of invasive ductal carcinoma of the breast: clinicopathological significance of fibrotic focus. Pathol Int, 50(4): 263–272

    PubMed  CAS  Google Scholar 

  • Heidelberger C, Chaudhuri N K, Danneberg P, Mooren D, Griesbach L, Duschinsky R, Schnitzer R J, Pleven E, Scheiner J (1957). Fluorinated pyrimidines, a new class of tumour-inhibitory compounds. Nature, 179(4561): 663–666

    PubMed  CAS  Google Scholar 

  • Hembruff S L, Jokar I, Yang L, Cheng N (2010). Loss of transforming growth factor-beta signaling in mammary fibroblasts enhances CCL2 secretion to promote mammary tumor progression through macrophage-dependent and-independent mechanisms. Neoplasia, 12(5): 425–433

    PubMed  CAS  PubMed Central  Google Scholar 

  • Hermann P C, Huber S L, Herrler T, Aicher A, Ellwart J W, Guba M, Bruns C J, Heeschen C (2007). Distinct populations of cancer stem cells determine tumor growth and metastatic activity in human pancreatic cancer. Cell Stem Cell, 1(3): 313–323

    PubMed  CAS  Google Scholar 

  • Herrera M, Herrera A, Domínguez G, Silva J, García V, García J M, Gómez I, Soldevilla B, Muñoz C, Provencio M, Campos-Martin Y, García de Herreros A, Casal I, Bonilla F, Peña C (2013). Cancerassociated fibroblast and M2 macrophage markers together predict outcome in colorectal cancer patients. Cancer Sci, 104(4): 437–444

    PubMed  CAS  Google Scholar 

  • Hidalgo M (2010). Pancreatic cancer. N Engl J Med, 362(17): 1605–1617

    PubMed  CAS  Google Scholar 

  • Holohan C, Van Schaeybroeck S, Longley D B, Johnston P G (2013). Cancer drug resistance: an evolving paradigm. Nat Rev Cancer, 13(10): 714–726

    PubMed  CAS  Google Scholar 

  • Hong L Z, Wei X W, Chen J F, Shi Y (2013). Overexpression of periostin predicts poor prognosis in non-small cell lung cancer. Oncol Lett, 6(6):1595–1603

    PubMed  CAS  PubMed Central  Google Scholar 

  • Ibarra-Drendall C, Dietze E C, Seewaldt V L (2011). Metabolic syndrome and breast cancer risk: Is there a role for metformin? Current Breast Cancer Rep, 3(3): 142–150

    CAS  Google Scholar 

  • Ilmonen S, Jahkola T, Turunen J P, Muhonen T, Asko-Seljavaara S (2004). Tenascin-C in primary malignant melanoma of the skin. Histopathology, 45(4): 405–411

    PubMed  CAS  Google Scholar 

  • Jahkola T, Toivonen T, Virtanen I, von Smitten K, Nordling S, von Boguslawski K, Haglund C, Nevanlinna H, Blomqvist C (1998). Tenascin-C expression in invasion border of early breast cancer: a predictor of local and distant recurrence. Br J Cancer, 78(11): 1507–1513

    PubMed  CAS  PubMed Central  Google Scholar 

  • Jin J, Huang M, Wei H L, Liu G T (2002). Mechanism of 5-fluorouracil required resistance in human hepatocellular carcinoma cell line Bel (7402). World J Gastroenterol, 8(6): 1029–1034

    PubMed  CAS  Google Scholar 

  • Kahn N, Meister M, Eberhardt R, Muley T, Schnabel P A, Bender C, Johannes M, Keitel D, Sultmann H, Herth F J, Kuner R (2012). Early detection of lung cancer by molecular markers in endobronchial epithelial-lining fluid. J Thoracic Oncol, 7(6): 1001–1008

    CAS  Google Scholar 

  • Kalluri R, Zeisberg M (2006). Fibroblasts in cancer. Nat Rev Cancer, 6(5): 392–401

    PubMed  CAS  Google Scholar 

  • Kaseda K, Ishii G, Aokage K, Takahashi A, Kuwata T, Hishida T, Yoshida J, Kohno M, Nagai K, Ochiai A (2013). Identification of intravascular tumor microenvironment features predicting the recurrence of pathological stage I lung adenocarcinoma. Cancer Sci, 104(9): 1262–1269

    PubMed  CAS  Google Scholar 

  • Kawashiri S, Tanaka A, Noguchi N, Hase T, Nakaya H, Ohara T, Kato K, Yamamoto E (2009). Significance of stromal desmoplasia and myofibroblast appearance at the invasive front in squamous cell carcinoma of the oral cavity. Head Neck, 31(10): 1346–1353

    PubMed  Google Scholar 

  • Keizer H G, Schuurhuis G J, Broxterman H J, Lankelma J, Schoonen W G, van Rijn J, Pinedo HM, Joenje H (1989). Correlation of multidrug resistance with decreased drug accumulation, altered subcellular drug distribution, and increased P-glycoprotein expression in cultured SW-1573 human lung tumor cells. Cancer Res, 49(11): 2988–2993

    PubMed  CAS  Google Scholar 

  • Kemp L E, Mulloy B, Gherardi E (2006). Signalling by HGF/SF and Met: the role of heparan sulphate co-receptors. Biochem Soc Trans, 34(Pt 3): 414–417

    PubMed  CAS  Google Scholar 

  • Khunamornpong S, Lekawanvijit S, Settakorn J, Sukpan K, Suprasert P, Siriaunkgul S (2013). Prognostic model in patients with early-stage squamous cell carcinoma of the uterine cervix: a combination of invasive margin pathological characteristics and lymphovascular space invasion. Asian Pac J Cancer Prev, 14(11): 6935–6940

    PubMed  Google Scholar 

  • Kii I, Nishiyama T, Li M, Matsumoto K, Saito M, Amizuka N, Kudo A (2010). Incorporation of tenascin-C into the extracellular matrix by periostin underlies an extracellular meshwork architecture. J Biol Chem, 285(3): 2028–2039

    PubMed  CAS  PubMed Central  Google Scholar 

  • Kitano H, Kageyama S, Hewitt S M, Hayashi R, Doki Y, Ozaki Y, Fujino S, Takikita M, Kubo H, Fukuoka J (2010). Podoplanin expression in cancerous stroma induces lymphangiogenesis and predicts lymphatic spread and patient survival. Arch Pathol Lab Med, 134(10): 1520–1527

    PubMed  CAS  Google Scholar 

  • Kojima M, Nakajima K, Ishii G, Saito N, Ochiai A (2010). Peritoneal elastic laminal invasion of colorectal cancer: the diagnostic utility and clinicopathologic relationship. Am J Surg Pathol, 34(9): 1351–1360

    PubMed  Google Scholar 

  • Kreuzaler P, Watson C J (2012). Killing a cancer: what are the alternatives? Nat Rev Cancer, 12(6): 411–424

    PubMed  CAS  Google Scholar 

  • Kucia M, Jankowski K, Reca R, Wysoczynski M, Bandura L, Allendorf D J, Zhang J, Ratajczak J, Ratajczak M Z (2004). CXCR4-SDF-1 signalling, locomotion, chemotaxis and adhesion. J Mol Histol, 35(3): 233–245

    PubMed  CAS  Google Scholar 

  • Kwon Y, Smith B D, Zhou Y, Kaufman M D, Godwin A K (2013). Effective inhibition of c-MET-mediated signaling, growth and migration of ovarian cancer cells is influenced by the ovarian tissue microenvironment. Oncogene

    Google Scholar 

  • Lari S A, Kuerer H M (2011). Biological Markers in DCIS and Risk of Breast Recurrence: A Systematic Review. J Cancer, 2: 232–261

    PubMed  PubMed Central  Google Scholar 

  • Lee S H, Kim H, Hwang J H, Lee H S, Cho J Y, Yoon Y S, Han H S (2012). Breast cancer resistance protein expression is associated with early recurrence and decreased survival in resectable pancreatic cancer patients. Pathol Int, 62(3): 167–175

    PubMed  Google Scholar 

  • Lemmon M A, and Schlessinger J (2010). Cell signaling by receptor tyrosine kinases. Cell, 141(7): 1117–1134

    PubMed  CAS  PubMed Central  Google Scholar 

  • Lengauer C, Kinzler KW, and Vogelstein B (1998). Genetic instabilities in human cancers. Nature, 396(6712): 643–649

    PubMed  CAS  Google Scholar 

  • Levina V, Marrangoni A M, DeMarco R, Gorelik E, Lokshin A E (2008). Drug-selected human lung cancer stem cells: cytokine network, tumorigenic and metastatic properties. PLoS ONE, 3(8): e3077

    PubMed  PubMed Central  Google Scholar 

  • Lhommé C, Joly F, Walker J L, Lissoni A A, Nicoletto MO, Manikhas G M, Baekelandt M M, Gordon A N, Fracasso P M, Mietlowski W L, Jones G J, Dugan M H (2008). Phase III study of valspodar (PSC 833) combined with paclitaxel and carboplatin compared with paclitaxel and carboplatin alone in patients with stage IV or suboptimally debulked stage III epithelial ovarian cancer or primary peritoneal cancer. J Clin Oncol, 26(16): 2674–2682

    PubMed  Google Scholar 

  • Li L, Dragulev B, Zigrino P, Mauch C, Fox J W (2009). The invasive potential of human melanoma cell lines correlates with their ability to alter fibroblast gene expression in vitro and the stromal microenvironment in vivo. Int J Cancer, 125(8): 1796–1804

    PubMed  CAS  Google Scholar 

  • Li M, Li C, Li D, Xie Y, Shi J, Li G, Guan Y, Li M, Zhang P, Peng F, Xiao Z, Chen Z (2012). Periostin, a stroma-associated protein, correlates with tumor invasiveness and progression in nasopharyngeal carcinoma. Clin Exp Metastasis, 29(8): 865–877

    PubMed  Google Scholar 

  • Liao D, Luo Y, Markowitz D, Xiang R, Reisfeld R A (2009). Cancer associated fibroblasts promote tumor growth and metastasis by modulating the tumor immune microenvironment in a 4T1 murine breast cancer model. PLoS ONE, 4(11): e7965

    PubMed  PubMed Central  Google Scholar 

  • Lim K P, Cirillo N, Hassona Y, Wei W, Thurlow J K, Cheong S C, Pitiyage G, Parkinson E K, Prime S S (2011). Fibroblast gene expression profile reflects the stage of tumour progression in oral squamous cell carcinoma. J Pathol, 223(4): 459–469

    PubMed  Google Scholar 

  • Liu R, Li J, Xie K, Zhang T, Lei Y, Chen Y, Zhang L, Huang K, Wang K, Wu H, Wu M, Nice E C, Huang C, Wei Y (2013). FGFR4 promotes stroma-induced epithelial-to-mesenchymal transition in colorectal cancer. Cancer Res, 73(19): 5926–5935

    PubMed  CAS  Google Scholar 

  • Loebinger M R, Giangreco A, Groot K R, Prichard L, Allen K, Simpson C, Bazley L, Navani N, Tibrewal S, Davies D, Janes S M (2008). Squamous cell cancers contain a side population of stem-like cells that are made chemosensitive by ABC transporter blockade. Br J Cancer, 98(2): 380–387

    PubMed  CAS  PubMed Central  Google Scholar 

  • Lotti F, Jarrar A M, Pai R K, Hitomi M, Lathia J, Mace A, Gantt G A Jr, Sukhdeo K, DeVecchio J, Vasanji A, Leahy P, Hjelmeland A B, Kalady M F, Rich J N (2013). Chemotherapy activates cancerassociated fibroblasts to maintain colorectal cancer-initiating cells by IL-17A. J Exp Med, 210(13): 2851–2872

    PubMed  CAS  Google Scholar 

  • Lu Y, Chen Q, Corey E, Xie W, Fan J, Mizokami A, Zhang J (2009). Activation of MCP-1/CCR2 axis promotes prostate cancer growth in bone. Clin Exp Metastasis, 26(2): 161–169

    PubMed  Google Scholar 

  • Lu Y, Xiao G, Galson D L, Nishio Y, Mizokami A, Keller E T, Yao Z, Zhang J (2007). PTHrP-induced MCP-1 production by human bone marrow endothelial cells and osteoblasts promotes osteoclast differentiation and prostate cancer cell proliferation and invasion in vitro. Int J Cancer, 121(4): 724–733

    PubMed  CAS  Google Scholar 

  • Lv Y, Wang W, Jia W D, Sun Q K, Li J S, Ma J L, Liu W B, Zhou H C, Ge Y S, Yu J H, Xia H H, Xu G L (2013). High-level expression of periostin is closely related to metastatic potential and poor prognosis of hepatocellular carcinoma. Med Oncol, 30(1): 385

    PubMed  Google Scholar 

  • MacDonald B T, Tamai K, He X (2009). Wnt/beta-catenin signaling: components, mechanisms, and diseases. Dev Cell, 17(1): 9–26

    PubMed  CAS  PubMed Central  Google Scholar 

  • Malanchi I, Santamaria-Martinez A, Susanto E, Peng H, Lehr H A, Delaloye J F, Huelsken J (2012). Interactions between cancer stem cells and their niche govern metastatic colonization. Nature, 481(7379): 85–89

    CAS  Google Scholar 

  • Malofeeva E V, Domanitskaya N, Gudima M, Hopper-Borge E A (2012). Modulation of the ATPase and transport activities of broadacting multidrug resistance factor ABCC10 (MRP7). Cancer Res, 72(24): 6457–6467

    PubMed  CAS  PubMed Central  Google Scholar 

  • Marsh D, Suchak K, Moutasim K A, Vallath S, Hopper C, Jerjes W, Upile T, Kalavrezos N, Violette S M, Weinreb P H, Chester K A, Chana J S, Marshall J F, Hart I R, Hackshaw A K, Piper K, Thomas G J (2011). Stromal features are predictive of disease mortality in oral cancer patients. J Pathol, 223(4): 470–481

    PubMed  CAS  Google Scholar 

  • Masuoka M, Shiraishi H, Ohta S, Suzuki S, Arima K, Aoki S, Toda S, Inagaki N, Kurihara Y, Hayashida S, Takeuchi S, Koike K, Ono J, Noshiro H, Furue M, Conway S J, Narisawa Y, Izuhara K (2012). Periostin promotes chronic allergic inflammation in response to Th2 cytokines. J Clin Invest, 122(7): 2590–2600

    PubMed  CAS  PubMed Central  Google Scholar 

  • Mertens J C, Fingas C D, Christensen J D, Smoot R L, Bronk S F, Werneburg NW, Gustafson MP, Dietz A B, Roberts L R, Sirica A E, Gores G J (2013). Therapeutic effects of deleting cancer-associated fibroblasts in cholangiocarcinoma. Cancer Res, 73(2): 897–907

    PubMed  CAS  PubMed Central  Google Scholar 

  • Mhawech-Fauceglia P, Wang D, Samrao D, Kim G, Lawrenson K, Meneses T, Liu S, Yessaian A, Pejovic T (2013). Clinical implications of marker expression of carcinoma-associated Fibroblasts (CAFs) in patients with epithelial ovarian carcinoma after treatment with neoadjuvant chemotherapy. Cancer Microenviron, PMID: 24214412

    Google Scholar 

  • Millward M J, Cantwell B M, Munro N C, Robinson A, Corris P A, Harris A L (1993). Oral verapamil with chemotherapy for advanced non-small cell lung cancer: a randomised study. Br J Cancer, 67(5): 1031–1035

    PubMed  CAS  PubMed Central  Google Scholar 

  • Mueller L, von Seggern L, Schumacher J, Goumas F, Wilms C, Braun F, Broering D C (2010). TNF-alpha similarly induces IL-6 and MCP-1 in fibroblasts from colorectal liver metastases and normal liver fibroblasts. Biochem Biophys Res Commun, 397(3): 586–591

    PubMed  CAS  Google Scholar 

  • Naldini L, Weidner K M, Vigna E, Gaudino G, Bardelli A, Ponzetto C, Narsimhan R P, Hartmann G, Zarnegar R, Michalopoulos G K, et al (1991). Scatter factor and hepatocyte growth factor are indistinguishable ligands for the MET receptor. EMBO J, 10(10): 2867–2878

    PubMed  CAS  PubMed Central  Google Scholar 

  • Naumov G N, Townson J L, MacDonald I C, Wilson S M, Bramwell V H, Groom A C, Chambers A F (2003). Ineffectiveness of doxorubicin treatment on solitary dormant mammary carcinoma cells or latedeveloping metastases. Breast Cancer Res Treat, 82(3): 199–206

    PubMed  CAS  Google Scholar 

  • Nicolo G, Salvi S, Oliveri G, Borsi L, Castellani P, Zardi L (1990). Expression of tenascin and of the ED-B containing oncofetal fibronectin isoform in human cancer. Cell Differ Dev, 32(3): 401–408

    PubMed  CAS  Google Scholar 

  • Nuzzo P V, Rubagotti A, Zinoli L, Ricci F, Salvi S, Boccardo S, Boccardo F (2012). Prognostic value of stromal and epithelial periostin expression in human prostate cancer: correlation with clinical pathological features and the risk of biochemical relapse or death. BMC Cancer, 12(1): 625

    PubMed  PubMed Central  Google Scholar 

  • O’Connell J T, Sugimoto H, Cooke V G, MacDonald B A, Mehta A I, LeBleu V S, Dewar R, Rocha R M, Brentani R R, Resnick M B, Neilson E G, Zeisberg M, Kalluri R (2011). VEGF-A and Tenascin-C produced by S100A4 + stromal cells are important for metastatic colonization. Proc Natl Acad Sci USA, 108(38): 16002–16007

    PubMed  PubMed Central  Google Scholar 

  • Oguri T, Ozasa H, Uemura T, Bessho Y, Miyazaki M, Maeno K, Maeda H, Sato S, Ueda R (2008). MRP7/ABCC10 expression is a predictive biomarker for the resistance to paclitaxel in non-small cell lung cancer. Mol Cancer Ther, 7(5): 1150–1155

    PubMed  CAS  Google Scholar 

  • Ohira S, Sasaki M, Harada K, Sato Y, Zen Y, Isse K, Kozaka K, Ishikawa A, Oda K, Nimura Y, Nakanuma Y (2006). Possible regulation of migration of intrahepatic cholangiocarcinoma cells by interaction of CXCR4 expressed in carcinoma cells with tumor necrosis factor-alpha and stromal-derived factor-1 released in stroma. Am J Pathol, 168(4): 1155–1168

    PubMed  CAS  PubMed Central  Google Scholar 

  • Ohnishi T, Daikuhara Y (2003). Hepatocyte growth factor/scatter factor in development, inflammation and carcinogenesis: its expression and role in oral tissues. Arch Oral Biol, 48(12): 797–804

    PubMed  CAS  Google Scholar 

  • Ohno Y, Izumi M, Yoshioka K, Ohori M, Yonou H, Tachibana M (2008). Prognostic significance of tenascin-C expression in clear cell renal cell carcinoma. Oncol Rep, 20(3): 511–516

    PubMed  Google Scholar 

  • Olumi A F, Grossfeld G D, Hayward SW, Carroll P R, Tlsty T D, Cunha G R (1999). Carcinoma-associated fibroblasts direct tumor progression of initiated human prostatic epithelium. Cancer Res, 59(19): 5002–5011

    PubMed  CAS  Google Scholar 

  • Orend G, Chiquet-Ehrismann R (2006). Tenascin-C induced signaling in cancer. Cancer Lett, 244(2): 143–163

    PubMed  CAS  Google Scholar 

  • Orimo A, Gupta P B, Sgroi D C, Arenzana-Seisdedos F, Delaunay T, Naeem R, Carey V J, Richardson A L, Weinberg R A (2005). Stromal fibroblasts present in invasive human breast carcinomas promote tumor growth and angiogenesis through elevated SDF-1/CXCL12 secretion. Cell, 121(3): 335–348

    PubMed  CAS  Google Scholar 

  • Oskarsson T, Acharyya S, Zhang X H, Vanharanta S, Tavazoie S F, Morris P G, Downey R J, Manova-Todorova K, Brogi E, Massagué J (2011). Breast cancer cells produce tenascin C as a metastatic niche component to colonize the lungs. Nat Med, 17(7): 867–874

    PubMed  CAS  Google Scholar 

  • Ostman A, Augsten M (2009). Cancer-associated fibroblasts and tumor growth-bystanders turning into key players. Curr Opin Genet Dev, 19(1): 67–73

    PubMed  Google Scholar 

  • Parr C, Jiang W G (2001). Expression of hepatocyte growth factor/ scatter factor, its activator, inhibitors and the c-Met receptor in human cancer cells. Int J Oncol, 19(4): 857–863

    PubMed  CAS  Google Scholar 

  • Paulsson J, Sjöblom T, Micke P, Pontén F, Landberg G, Heldin C H, Bergh J, Brennan D J, Jirström K, Ostman A (2009). Prognostic significance of stromal platelet-derived growth factor beta-receptor expression in human breast cancer. Am J Pathol, 175(1): 334–341

    PubMed  PubMed Central  Google Scholar 

  • Peled A, and Tavor S (2013). Role of CXCR4 in the pathogenesis of acute myeloid leukemia. Theranostics 3(1), 34–39.

    PubMed  CAS  PubMed Central  Google Scholar 

  • Pezzolo A, Parodi F, Marimpietri D, Raffaghello L, Cocco C, Pistorio A, Mosconi M, Gambini C, Cilli M, Deaglio S, Malavasi F, Pistoia V (2011). Oct-4 +/Tenascin C + neuroblastoma cells serve as progenitors of tumor-derived endothelial cells. Cell Res, 21(10): 1470–1486

    PubMed  CAS  PubMed Central  Google Scholar 

  • Polanska U M, Orimo A (2013). Carcinoma-associated fibroblasts: nonneoplastic tumour-promoting mesenchymal cells. J Cell Physiol, 228(8): 1651–1657

    PubMed  CAS  Google Scholar 

  • Polyak K, Kalluri R (2010). The role of the microenvironment in mammary gland development and cancer. Cold Spring Harb Perspect Biol, 2(11): a003244

    PubMed  CAS  PubMed Central  Google Scholar 

  • Qian B Z, Li J, Zhang H, Kitamura T, Zhang J, Campion L R, Kaiser E A, Snyder L A, and Pollard J W (2011). CCL2 recruits inflammatory monocytes to facilitate breast-tumour metastasis. Nature 475(7355), 222–225.

    PubMed  CAS  PubMed Central  Google Scholar 

  • Qian D Z, Rademacher B L, Pittsenbarger J, Huang C Y, Myrthue A, Higano C S, Garzotto M, Nelson P S, and Beer T M (2010). CCL2 is induced by chemotherapy and protects prostate cancer cells from docetaxel-induced cytotoxicity. Prostate, 70(4): 433–442

    PubMed  CAS  PubMed Central  Google Scholar 

  • Roberts P J, and Der C J (2007). Targeting the Raf-MEK-ERK mitogenactivated protein kinase cascade for the treatment of cancer. Oncogene, 26(22): 3291–3310

    PubMed  CAS  Google Scholar 

  • Roca H, Varsos Z, Pienta K J (2008). CCL2 protects prostate cancer PC3 cells from autophagic death via phosphatidylinositol 3-kinase/AKTdependent survivin up-regulation. J Biol Chem, 283(36): 25057–25073

    PubMed  CAS  PubMed Central  Google Scholar 

  • Roninson I B (2003). Tumor cell senescence in cancer treatment. Cancer Res, 63(11): 2705–2715

    PubMed  CAS  Google Scholar 

  • Samaratunga H, Fairweather P, Purdie D (2005). Significance of stromal reaction patterns in invasive urothelial carcinoma. Am J Clin Pathol, 123(6): 851–857

    PubMed  Google Scholar 

  • Sankala H M, Hait N C, Paugh S W, Shida D, Lépine S, Elmore L W, Dent P, Milstien S, Spiegel S (2007). Involvement of sphingosine kinase 2 in p53-independent induction of p21 by the chemotherapeutic drug doxorubicin. Cancer Res, 67(21): 10466–10474

    PubMed  CAS  Google Scholar 

  • Schoppmann S F, Jesch B, Riegler M F, Maroske F, Schwameis K, Jomrich G, Birner P (2013). Podoplanin expressing cancer associated fibroblasts are associated with unfavourable prognosis in adenocarcinoma of the esophagus. Clin Exp Metastasis, 30(4): 441–446

    PubMed  CAS  Google Scholar 

  • Seslar S P, Nakamura T, Byers S W (1993). Regulation of fibroblast hepatocyte growth factor/scatter factor expression by human breast carcinoma cell lines and peptide growth factors. Cancer Res, 53(6): 1233–1238

    PubMed  CAS  Google Scholar 

  • Shimao Y, Nabeshima K, Inoue T, Koono M (1999). Role of fibroblasts in HGF/SF-induced cohort migration of human colorectal carcinoma cells: fibroblasts stimulate migration associated with increased fibronectin production via upregulated TGF-beta1. Int J Cancer, 82(3): 449–458

    PubMed  CAS  Google Scholar 

  • Shinde A V, Frangogiannis N G (2013). Fibroblasts in myocardial infarction: A role in inflammation and repair. J Mol Cell Cardiol, doi: 10.1016/j.yjmcc.2013.11.015

    Google Scholar 

  • Siegsmund M J, Kreukler C, Steidler A, Nebe T, Köhrmann K U, Alken P (1997). Multidrug resistance in androgen-independent growing rat prostate carcinoma cells is mediated by P-glycoprotein. Urol Res, 25(1): 35–41

    PubMed  CAS  Google Scholar 

  • Silzle T, Kreutz M, Dobler M A, Brockhoff G, Knuechel R, Kunz-Schughart L A (2003). Tumor-associated fibroblasts recruit blood monocytes into tumor tissue. Eur J Immunol, 33(5): 1311–1320

    PubMed  CAS  Google Scholar 

  • Smith N Z (2012). Treating metastatic breast cancer with systemic chemotherapies: current trends and future perspectives. Clin J Oncol Nurs, 16(2): E33–E43

    PubMed  Google Scholar 

  • Soon P S, Kim E, Pon C K, Gill A J, Moore K, Spillane A J, Benn D E, Baxter R C (2013). Breast cancer-associated fibroblasts induce epithelial-to-mesenchymal transition in breast cancer cells. Endocr Relat Cancer, 20(1): 1–12

    PubMed  CAS  Google Scholar 

  • Stoker M, Gherardi E, Perryman M, Gray J (1987). Scatter factor is a fibroblast-derived modulator of epithelial cell mobility. Nature, 327(6119): 239–242

    PubMed  CAS  Google Scholar 

  • Stoker M, Perryman M (1985). An epithelial scatter factor released by embryo fibroblasts. J Cell Sci, 77: 209–223

    PubMed  CAS  Google Scholar 

  • Straussman R, Morikawa T, Shee K, Barzily-Rokni M, Qian Z R, Du J, Davis A, Mongare M M, Gould J, Frederick D T, Cooper Z A, Chapman P B, Solit D B, Ribas A, Lo R S, Flaherty K T, Ogino S, Wargo J A, Golub T R (2012). Tumour micro-environment elicits innate resistance to RAF inhibitors through HGF secretion. Nature, 487(7408): 500–504

    PubMed  CAS  PubMed Central  Google Scholar 

  • Stupack D G, Cheresh D A (2002). Get a ligand, get a life: integrins, signaling and cell survival. J Cell Sci, 115(Pt 19): 3729–3738

    PubMed  CAS  Google Scholar 

  • Sturm I, Bosanquet A G, Hermann S, Güner D, Dörken B, Daniel P T (2003). Mutation of p53 and consecutive selective drug resistance in B-CLL occurs as a consequence of prior DNA-damaging chemotherapy. Cell Death Differ, 10(4): 477–484

    PubMed  CAS  Google Scholar 

  • Sun Y, Campisi J, Higano C, Beer T M, Porter P, Coleman I, True L, Nelson P S (2012). Treatment-induced damage to the tumor microenvironment promotes prostate cancer therapy resistance through WNT16B. Nat Med, 18(9): 1359–1368

    PubMed  CAS  PubMed Central  Google Scholar 

  • Takeuchi K, Ito F (2011). Receptor tyrosine kinases and targeted cancer therapeutics. Biol Pharm Bull, 34(12): 1774–1780

    PubMed  CAS  Google Scholar 

  • Taylor C W, Dalton W S, Parrish P R, Gleason M C, Bellamy W T, Thompson F H, Roe D J, Trent J M (1991). Different mechanisms of decreased drug accumulation in doxorubicin and mitoxantrone resistant variants of the MCF7 human breast cancer cell line. Br J Cancer, 63(6): 923–929

    PubMed  CAS  PubMed Central  Google Scholar 

  • Tegze B, Szállási Z, Haltrich I, Pénzváltó Z, Tóth Z, Likó I, Gyorffy B (2012). Parallel evolution under chemotherapy pressure in 29 breast cancer cell lines results in dissimilar mechanisms of resistance. PLoS ONE, 7(2): e30804

    PubMed  CAS  PubMed Central  Google Scholar 

  • Thomas D, Vadas M, Lopez A (2004). Regulation of haematopoiesis by growth factors-emerging insights and therapies. Expert Opin Biol Ther, 4(6): 869–879

    PubMed  CAS  Google Scholar 

  • Tjomsland V, Niklasson L, Sandström P, Borch K, Druid H, Bratth-ll C, Messmer D, Larsson M, Spångeus A (2011). The desmoplastic stroma plays an essential role in the accumulation and modulation of infiltrated immune cells in pancreatic adenocarcinoma. Clin Dev Immunol, 2011: 212810

    PubMed  PubMed Central  Google Scholar 

  • Torres S, Bartolomé R A, Mendes M, Barderas R, Fernandez-AceñeroM J, Peláez-García A, Peña C, Lopez-Lucendo M, Villar-Vázquez R, de Herreros A G, Bonilla F, Casal J I (2013). Proteome profiling of cancer-associated fibroblasts identifies novel proinflammatory signatures and prognostic markers for colorectal cancer. Clin Cancer Res, 19(21): 6006–6019

    PubMed  CAS  Google Scholar 

  • Tsujino T, Seshimo I, Yamamoto H, Ngan C Y, Ezumi K, Takemasa I, Ikeda M, Sekimoto M, Matsuura N, Monden M (2007). Stromal myofibroblasts predict disease recurrence for colorectal cancer. Clin Cancer Res, 13(7): 2082–2090

    PubMed  CAS  Google Scholar 

  • Tsuyada A, Chow A, Wu J, Somlo G, Chu P, Loera S, Luu T, Li A X, Wu X, Ye W, Chen S, Zhou W, Yu Y, Wang Y Z, Ren X, Li H, Scherle P, Kuroki Y, Wang S E (2012). CCL2 mediates cross-talk between cancer cells and stromal fibroblasts that regulates breast cancer stem cells. Cancer Res, 72(11): 2768–2779

    PubMed  CAS  PubMed Central  Google Scholar 

  • Uchida D, Kawamata H, Omotehara F, Nakashiro Ki, Kimura-Yanagawa T, Hino S, Begum N M, Hoque M O, Yoshida H, Sato M, Fujimori T (2001). Role of HGF/c-met system in invasion and metastasis of oral squamous cell carcinoma cells in vitro and its clinical significance. Int J Cancer, 93(4): 489–496

    PubMed  CAS  Google Scholar 

  • van Leenders G J, Sookhlall R, TeubelW J, de Ridder C M, Reneman S, Sacchetti A, Vissers K J, van Weerden W, Jenster G (2011). Activation of c-MET induces a stem-like phenotype in human prostate cancer. PLoS ONE, 6(11): e26753

    PubMed  PubMed Central  Google Scholar 

  • Vermeulen L, De Sousa E Melo F, van der Heijden M, Cameron K, de Jong J H, Borovski T, Tuynman J B, Todaro M, Merz C, Rodermond H, Sprick M R, Kemper K, Richel D J, Stassi G, Medema J P (2010). Wnt activity defines colon cancer stem cells and is regulated by the microenvironment. Nat Cell Biol, 12(5): 468–476

    PubMed  CAS  Google Scholar 

  • Wang B, Liu K, Lin H Y, Bellam N, Ling S, LinW C (2010). 14-3-3Tau regulates ubiquitin-independent proteasomal degradation of p21, a novel mechanism of p21 downregulation in breast cancer. Mol Cell Biol, 30(6): 1508–1527

    PubMed  CAS  PubMed Central  Google Scholar 

  • Wang P, Nishitani M A, Tanimoto S, Kishimoto T, Fukumori T, Takahashi M, and Kanayama H O (2007). Bladder cancer cell invasion is enhanced by cross-talk with fibroblasts through hepatocyte growth factor. Urology, 69(4): 780–784

    PubMed  Google Scholar 

  • Wang Q, Fiel M I, Blank S, Luan W, Kadri H, Kim K W, Manizate F, Rosenblatt A G, Labow D M, Schwartz M E, Hiotis S P (2013). Impact of liver fibrosis on prognosis following liver resection for hepatitis B-associated hepatocellular carcinoma. Br J Cancer, 109(3): 573–581

    PubMed  CAS  Google Scholar 

  • Wang W, Li Q, Yamada T, Matsumoto K, Matsumoto I, Oda M, Watanabe G, Kayano Y, Nishioka Y, Sone S, Yano S (2009). Crosstalk to stromal fibroblasts induces resistance of lung cancer to epidermal growth factor receptor tyrosine kinase inhibitors. Clin Cancer Res, 15(21): 6630–6638

    PubMed  CAS  Google Scholar 

  • Wartenberg M, Frey C, Diedershagen H, Ritgen J, Hescheler J, Sauer H (1998). Development of an intrinsic P-glycoprotein-mediated doxorubicin resistance in quiescent cell layers of large, multicellular prostate tumor spheroids. Int J Cancer, 75(6): 855–863

    PubMed  CAS  Google Scholar 

  • White G E, Iqbal A J, Greaves D R (2013). CC chemokine receptors and chronic inflammation-therapeutic opportunities and pharmacological challenges. Pharmacol Rev, 65(1): 47–89

    PubMed  CAS  Google Scholar 

  • Wilson K J, Mill C, Lambert S, Buchman J, Wilson T R, Hernandez-Gordillo V, Gallo R M, Ades L M, Settleman J, Riese D J 2nd (2012a). EGFR ligands exhibit functional differences in models of paracrine and autocrine signaling. Growth Factors, 30(2): 107–116

    PubMed  CAS  PubMed Central  Google Scholar 

  • Wilson T R, Fridlyand J, Yan Y, Penuel E, Burton L, Chan E, Peng J, Lin E, Wang Y, Sosman J, Ribas A, Li J, Moffat J, Sutherlin D P, Koeppen H, Merchant M, Neve R, and Settleman J (2012b). Widespread potential for growth-factor-driven resistance to anticancer kinase inhibitors. Nature, 487(7408): 505–509

    PubMed  CAS  PubMed Central  Google Scholar 

  • Wishart G C, Bissett D, Paul J, Jodrell D, Harnett A, Habeshaw T, Kerr D J, Macham M A, Soukop M, Leonard R C, et al (1994). Quinidine as a resistance modulator of epirubicin in advanced breast cancer: mature results of a placebo-controlled randomized trial. J Clin Oncol, 12(9): 1771–1777

    PubMed  CAS  Google Scholar 

  • Wong M P, Cheung K N, Yuen S T, Fu K H, Chan A S, Leung S Y, Chung L P (1998). Monocyte chemoattractant protein-1 (MCP-1) expression in primary lymphoepithelioma-like carcinomas (LELCs) of the lung. J Pathol, 186(4): 372–377

    PubMed  CAS  Google Scholar 

  • Wu K J (2011). Direct activation of Bmi1 by Twist1: implications in cancer stemness, epithelial-mesenchymal transition, and clinical significance. Chang Gung Med J, 34(3): 229–238

    PubMed  Google Scholar 

  • Wu MH, Hong H C, Hong TM, Chiang WF, Jin Y T, Chen Y L (2011). Targeting galectin-1 in carcinoma-associated fibroblasts inhibits oral squamous cell carcinoma metastasis by downregulating MCP-1/CCL2 expression. Clin Cancer Res, 17(6): 1306–1316

    PubMed  CAS  Google Scholar 

  • Xiong J, Balcioglu H E, Danen E H (2013). Integrin signaling in control of tumor growth and progression. Int J Biochem Cell Biol, 45(5): 1012–1015

    PubMed  CAS  Google Scholar 

  • Xu D, Xu H, Ren Y, Liu C, Wang X, Zhang H, Lu P (2012). Cancer stem cell-related gene periostin: a novel prognostic marker for breast cancer. PLoS ONE, 7(10): e46670

    PubMed  CAS  PubMed Central  Google Scholar 

  • Yamada T, Matsumoto K, Wang W, Li Q, Nishioka Y, Sekido Y, Sone S, Yano S (2010). Hepatocyte growth factor reduces susceptibility to an irreversible epidermal growth factor receptor inhibitor in EGFRT790M mutant lung cancer. Clin Cancer Res, 16(1): 174–183

    PubMed  CAS  Google Scholar 

  • Yasunaga M, Yamasaki F, Tokunaga O, Iwasaka T (2003). Endometrial carcinomas with lymph node involvement: novel histopathologic factors for predicting prognosis. Int J Gynecol Pathol, 22(4): 341–346

    PubMed  Google Scholar 

  • Yoshida S, Harada T, Iwabe T, Taniguchi F, Fujii A, Sakamoto Y, Yamauchi N, Shiota G, Terakawa N (2002). Induction of hepatocyte growth factor in stromal cells by tumor-derived basic fibroblast growth factor enhances growth and invasion of endometrial cancer. J Clin Endocrinol Metab, 87(5): 2376–2383

    PubMed  CAS  Google Scholar 

  • Yu S, Xia S, Yang D, Wang K, Yeh S, Gao Z, Chang C (2013). Androgen receptor in human prostate cancer-associated fibroblasts promotes prostate cancer epithelial cell growth and invasion. Med Oncol, 30(3): 674

    PubMed  Google Scholar 

  • Zhang J, Yang P L, Gray N S (2009). Targeting cancer with small molecule kinase inhibitors. Nat Rev Cancer, 9(1): 28–39

    PubMed  Google Scholar 

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  1. Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, KS, 66160, USA

    Wei Bin Fang, Min Yao & Nikki Cheng

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Fang, W.B., Yao, M. & Cheng, N. Priming cancer cells for drug resistance: role of the fibroblast niche. Front. Biol. 9, 114–126 (2014). https://doi.org/10.1007/s11515-014-1300-8

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