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Anti-Tumor Effects of TRAIL-Expressing Mesenchymal Stromal Cells in a Mouse Xenograft Model of Human Mesothelioma

Sage, E; Janes, SM; (2015) Anti-Tumor Effects of TRAIL-Expressing Mesenchymal Stromal Cells in a Mouse Xenograft Model of Human Mesothelioma. Cancer Gene Therapy , 22 (1) pp. 44-54. 10.1038/cgt.2014.68. Green open access

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Abstract

Malignant mesothelioma (MM) remains a highly deadly malignancy with poor treatment option. The MM cells further promote a highly inflammatory microenvironment which contributes to tumor initiation, development, severity, and propagation. We reasoned that the anti-inflammatory actions of mesenchymal stromal cells (MSCs) and further anti-tumor effects of MSCs engineered to over-express TNF-related apoptosis inducing ligand (TRAIL) protein (MSC-TRAIL) would effectively inhibit mesothelioma growth. Using a mouse xenograft model of intraperitoneal human mesothelioma, native mouse (mMSC) or human (hMSC) MSCs were administered either systemically (IV) or intraperitoneally (IP) at various times following tumor inoculation. Both mMSCs and hMSCs localized at sites of MM tumor growth in vivo and decreased local inflammation. Further, a trend towards decrease in tumor burden was observed. Parallel studies of in vitro exposure of nine primary human mesothelioma cell lines to mMSCs or hMSCs demonstrated reduced tumor cell migration. In contrast MSC-TRAIL exposure induced apoptosis of TRAIL sensitive MM cells in vitro and both mouse and human MSC-TRAIL significantly reduced the inflammatory tumor environment in vivo. Moreover human MSC-TRAIL administration significantly reduced peritoneal tumor burden in vivo and increased tumor cell apoptosis. These proof-of-concept studies suggest that TRAIL-expressing MSCs may be useful against malignant mesothelioma.

Type: Article
Title: Anti-Tumor Effects of TRAIL-Expressing Mesenchymal Stromal Cells in a Mouse Xenograft Model of Human Mesothelioma
Open access status: An open access version is available from UCL Discovery
DOI: 10.1038/cgt.2014.68
Publisher version: http://dx.doi.org/10.1038/cgt.2014.68
Language: English
Additional information: Authors of original research articles are encouraged to submit the author's version of the accepted paper (the unedited manuscript) to their funding body's archive, for public release six months after publication. In addition, authors are encouraged to archive this version of the manuscript in their institution's repositories and on their personal websites, also six months after the original publication. This is in line with NPG's self-archiving policy.
Keywords: Mesenchymal stromal cell, Malignant mesothelioma, Mouse model, Cell therapy
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Respiratory Medicine
URI: https://discovery.ucl.ac.uk/id/eprint/1453658
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