Article Text

Download PDFPDF

Original article
Systemic but not topical TRAIL-expressing mesenchymal stem cells reduce tumour growth in malignant mesothelioma
  1. Elizabeth K Sage1,
  2. Krishna K Kolluri1,
  3. Katrina McNulty1,
  4. Sofia Da Silva Lourenco1,
  5. Tammy L Kalber1,2,
  6. Katherine L Ordidge1,2,
  7. Derek Davies3,
  8. Y C Gary Lee4,
  9. Adam Giangreco1,
  10. Sam M Janes1
  1. 1Division of Medicine, Lungs for Living Research Centre, University College London, London, UK
  2. 2Division of Medicine and Institute of Child Health, UCL Centre of Advanced Biomedical Imaging, University College London, London, UK
  3. 3Flow Cytometry Laboratory, Cancer Research UK, London Research Institute, London, UK
  4. 4School of Medicine and Pharmacology, University of Western Australia, Sir Charles Gairdner Hospital, Perth, Australia
  1. Correspondence to Dr Sam M Janes, Lungs for Living Research Centre, UCL Respiratory, Rayne Building, 5 University Street, London WC1E 6JF, UK; s.janes{at}ucl.ac.uk

Abstract

Malignant pleural mesothelioma is a rare but devastating cancer of the pleural lining with no effective treatment. The tumour is often diffusely spread throughout the chest cavity, making surgical resection difficult, while systemic chemotherapy offers limited benefit. Bone marrow-derived mesenchymal stem cells (MSCs) home to and incorporate into tumour stroma, making them good candidates to deliver anticancer therapies. Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) is a pro-apoptotic molecule that selectively induces apoptosis in cancer cells, leaving healthy cells unaffected. We hypothesised that human MSCs expressing TRAIL (MSCTRAIL) would home to an in vivo model of malignant pleural mesothelioma and reduce tumour growth. Human MSCs transduced with a lentiviral vector encoding TRAIL were shown in vitro to kill multiple malignant mesothelioma cell lines as predicted by sensitivity to recombinant TRAIL (rTRAIL). In vivo MSC homing was delineated using dual fluorescence and bioluminescent imaging, and we observed that higher levels of MSC engraftment occur after intravenous delivery compared with intrapleural delivery of MSCs. Finally, we show that intravenous delivery of MSCTRAIL results in a reduction in malignant pleural mesothelioma tumour growth in vivo via an increase in tumour cell apoptosis.

  • Mesothelioma
  • Asbestos Induced Lung Disease
  • Lung Cancer
  • Occupational Lung Disease

This is an Open Access article distributed in accordance with the terms of the Creative Commons Attribution (CC BY 3.0) license, which permits others to distribute, remix, adapt and build upon this work, for commercial use, provided the original work is properly cited. See: http://creativecommons.org/licenses/by/3.0/

View Full Text

Statistics from Altmetric.com

Supplementary materials

  • Supplementary Data

    This web only file has been produced by the BMJ Publishing Group from an electronic file supplied by the author(s) and has not been edited for content.

    Files in this Data Supplement:

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.