Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Paper
  • Published:

Maspin – the most commonly-expressed gene of the 18q21.3 serpin cluster in lung cancer – is strongly expressed in preneoplastic bronchial lesions

Oncogene volume 22, pages 8677–8687 (2003)Cite this article

Abstract

Maspin, SCCA1/2 and hurpin were identified by cDNA microarray analyses as dramatically differentially expressed transcripts in primary non-small cell lung cancer (NSCLC). These sequences are located within a 10-gene serpin cluster on 18q21.3. Using comparative RT–PCR, we have investigated the expression of each of these serpins, including their flanking loci, in an independent NSCLC series. Whereas six of the genes (maspin, SCCA1, SCCA2, hurpin, megsin and pAI-2) were commonly differentially expressed in primary lesions, each significantly more often in squamous cell tumours, maspin was identified as the most frequently over-represented sequence in both squamous cell carcinoma and adenocarcinoma. Using a well-characterized monoclonal antibody, we have shown strong maspin expression in tumour protein extracts, detected multiple isoforms of the 42 kDa protein and shown that maspin is localized specifically to the tumour cells within neoplastic lesions. In contrast, most cells in non-neoplastic lung tissue appear not to express the gene, with the exception of the multipotent basal epithelial cells that line the bronchial airway. These reserve cells generally show strong predominantly nuclear localization of maspin. Strong nuclear expression of maspin within primary tumour cells is correlated with increased survival (P=0.05) and a longer remission duration (P=0.02) in resectable-staged patients. However, within the airways of cancer patients and somewhat in contrast to this observation, such expression was more frequently detected in the superficial cells of preneoplastic over non-neoplastic epithelia (P<0.0001), consistent with a role for the protein in early neoplasia.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5

Similar content being viewed by others

References

  • Abraham S, Zhang W, Greenberg N and Zhang M . (2003). J. Urol., 169, 1157–1161.

  • Bass R, Fernandez AM and Ellis V . (2002). J. Biol. Chem., 277, 46845–46848.

  • Betticher DC, Heighway J, Thatcher N and Hasleton PS . (1997). Br. J. Cancer, 75, 1761–1768.

  • Biliran Jr H and Sheng S . (2001). Cancer Res., 61, 8676–8682.

  • Borner MM, Brousset P, Pfanner-Meyer B, Bacchi M, Vonlanthen S, Hotz MA, Altermatt HJ, Schlaifer D, Reed JC and Betticher DC . (1999). Br. J. Cancer, 79, 952–958.

  • Bray F, Sankila R, Ferlay J and Parkin DM . (2002). Eur. J. Cancer, 38, 99–166.

  • Cataltepe S, Gornstein ER, Schick C, Kamachi Y, Chatson K, Fries J, Silverman GA and Upton MP . (2000). J. Histochem. Cytochem., 48, 113–122.

  • Champelovier P, Besse A, Boucard N, Simon A, Leroux D, Pinel N, Praloran V and Seigneurin D . (2002). Eur. Urol., 39, 343–348.

  • Duggan C, Kennedy S, Kramer MD, Barnes C, Elvin P, McDermott E, O'Higgins N and Duffy MJ . (1997). Br. J. Cancer, 76, 622–627.

  • Fujita T, Kiyama M, Tomizawa Y, Kohno T and Yokota J . (1999). Int. J. Oncol., 15, 927–934.

  • Hamada K, Shinomiya H, Asano Y, Kihana T, Iwamoto M, Hanakawa Y, Hashimoto K, Hirose S, Kyo S and Ito M . (2001). Biochim. Biophys. Acta, 19, 124–131.

  • Heighway J, Knapp T, Boyce L, Brennand S, Field JK, Betticher DC, Ratschiller D, Gugger M, Donovan M, Lasek A and Rickert P . (2002). Oncogene, 21, 7749–7763.

  • Heighway J, Betticher DC, Knapp T and Hoban PR . (2003). Methods in Molecular Medecine, 75, 291–304.

  • Jayakumar A, Kang Y, Frederick MJ, Pak SC, Henderson Y, Holton PR, Mitsudo K, Silverman GA, EL-Naggar AK, Bromme D and Clayman GL . (2003). Arch. Biochem. Biophys., 409, 367–374.

  • Kato H . (1992). Serological Cancer Markers. Sell S. (ed). Humana Press: Totowa, NJ, pp. 437–451.

    Book  Google Scholar 

  • Kishimoto H, Urade M, Hashimoto-Tamaoki T and Furuyama JI . (2001). Int. J. Oncol., 18, 297–303.

  • Maass N, Hojo T, Rosel F, Ikeda T, Jonat W and Nagasaki K . (2001a). Clin. Biochem., 34, 303–307.

  • Maass N, Teffner M, Rosel F, Pawaresch R, Jonat W, Nagasaki K and Rudolph P . (2001b). J. Pathol., 195, 321–326.

  • Miyata T, Inagi R, Nangaku M, Imasawa T, Sato M, Izuhara Y, Suzuki D, Yoshino A, Onogi H, Kimura M, Sugiyama S and Kurokawa K . (2002). J. Clin. Invest., 109, 585–593.

  • Mohsin SK, Zhang M, Clark GM and Allred DC . (2003). J. Pathol., 199, 432–435.

  • Mueller BM, Yu YB and Laug WE . (1995). Proc. Natl. Acad. Sci. USA, 92, 205–209.

  • Murakami A, Suminami Y, Sakaguchi Y, Nawata S, Numa F, Kishi F and Kato H . (2000). Tumour Biol., 21, 224–234.

  • Nakashima T, Pak SC, Silverman GA, Spring PM, Frederick MJ and Clayman GL . (2000). Biochim. Biophys. Acta, 1492, 441–446.

  • Pemberton PA, Wong DT, Gibson HL, Kiefer MC, Fitzpatrick PA, Sager R and Barr PJ . (1995). J. Biol. Chem., 270, 15832–15837.

  • Pezzella F, Turley H, Kuzu I, Tungekar MF, Dunnill MS, Pierce CB, Harris A, Gatter KC and Mason DY . (1993). N. Engl. J. Med., 329, 690–694.

  • Pierson CR, McGowen R, Grignon D, Sakr W, Dey J and Sheng S . (2002). Prostate, 53, 255–262.

  • Potempa J, Korzus E and Travis J . (1994). J. Biol. Chem., 269, 15957–15960.

  • Ratschiller D, Heighway J, Gugger M, Kappeler A, Pirnia F, Schmid RA, Borner MM and Betticher DC . (2003). J. Clin. Oncol. 21, 2085–2093.

  • Reis-Filho JS, Milanezi F and Schmitt FC . (2002). J. Pathol., 197, 272–273.

  • Schick C, Kamachi Y, Bartuski AJ, Cataltepe S, Schechter NM, Pemberton PA and Silverman GA . (1997). J. Biol. Chem., 272, 1849–1855.

  • Schick C, Pemberton PA, Shi GP, Kamachi Y, Cataltepe S, Bartuski AJ, Gornstein ER, Bromme D, Chapman HA and Silverman GA . (1998). Biochemistry, 37, 5258–5266.

  • Schneider SS, Schick, C, Fish KE, Miller E, Pena JC, Teter SD, Hui SM and Silverman GA . (1995). Proc. Natl. Acad. Sci. USA, 92, 3147–3151.

  • Shi HY, Zhang W, Liang R, Abraham S, Kittrell FS, Medina D and Zhang M . (2001). Cancer Res., 61, 6945–6951.

  • Sood AK, Fletcher MS, Gruman LM, Coffin JE, Jabbari S, Khalkhali-Ellis Z, Arbour N, Seftor EA and Hendrix MJ . (2002). Clin. Cancer Res., 8, 2924–2932.

  • Stenman J, Hedstrom J, Grenman R, Leivo I, Finne P, Palotie A and Orpana A . (2001). Int. J. Cancer, 95, 39–43.

  • Suminami Y, Kishi F, Sekiguchi K and Kato H . (1991). Biochem. Biophys. Res. Commun., 181, 51–58.

  • Travis W, Colby T and Corrin B et al. (1999). Histological Typing of Lung and Pleural Tumours. Springer: Berlin.

    Book  Google Scholar 

  • Umekita Y, Ohi Y, Sagara Y and Yoshida H . (2002). Int. J. Cancer, 100, 452–455.

  • Verspaget HW, Sier CF, Ganesh S, Griffioen G and Lamers CB . (1995). Eur. J. Cancer, 31, 1105–1109.

  • Yasumatsu R, Nakashima T, Hirakawa N, Kumamoto Y, Kuratomi Y, Tomita K and Komiyama S . (2001). Head Neck, 23, 962–966.

  • Zou Z, Anisowicz A, Hendrix MJ, Thor A, Neveu M, Sheng S, Rafidi K, Seftor E and Sager R . (1994). Science, 263, 526–529.

  • Zou Z, Gao C, Nagaich AK, Connell T, Saito S, Moul JW, Seth P, Appella E and Srivastava S . (2000). J. Biol. Chem., 275, 6051–6054.

Download references

Acknowledgements

We thank the clinical teams in Liverpool and Bern for their assistance in the collection and processing of patient tissues. We also thank the patients for allowing us to use such material for our research. This work was funded by the Roy Castle Lung Cancer Foundation, UK, the Swiss Cancer League (KFS-703-8-1998) and the Bernese Cancer League.

Author information

Authors and Affiliations

  1. Target Identification Group, Roy Castle International Centre for Lung Cancer Research, University of Liverpool, 200 London Rd, Liverpool, L3 9TA, UK

    Shirley L Smith, Suzanne G Watson & Jim Heighway

  2. Institute of Medical Oncology, University of Bern, Bern, 3010, Switzerland

    Daniel Ratschiller, Mathias Gugger & Daniel C Betticher

Authors
  1. Shirley L Smith
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Suzanne G Watson
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Daniel Ratschiller
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Mathias Gugger
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Daniel C Betticher
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Jim Heighway
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jim Heighway.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Smith, S., Watson, S., Ratschiller, D. et al. Maspin – the most commonly-expressed gene of the 18q21.3 serpin cluster in lung cancer – is strongly expressed in preneoplastic bronchial lesions. Oncogene 22, 8677–8687 (2003). https://doi.org/10.1038/sj.onc.1207127

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1207127

Keywords

This article is cited by

Search

Advanced search

Quick links