TRAIL-expressing mesenchymal stem cells kill the putative cancer stem cell population

Abstract

Background: Tumours contain stem-like, side population (SP) cells, which have increased tumorigenic potential, resistance to traditional therapies and may be responsible for treatment failures and relapse in patients. Methods: Mesenchymal stem cells (MSCs) were engineered to express the apoptotic ligand, TNF-related apoptosis-inducing ligand (TRAIL). Squamous (H357) and lung (A549) cancer cell lines were sorted into side and non-side populations (non-SP) by Hoechst flow cytometry. The survival and growth of both SP and non-SP cancer populations, in conjunction with TRAIL-expressing MSCs and mitoxantrone chemotherapy, were assessed by flow cytometry and colony forming ability. Results : Mesenchymal stem cells expressing TRAIL migrate to tumours and reduce the growth of primary cancers and metastases. This report demonstrates that these cells cause apoptosis, death and reduced colony formation of the SP of squamous and adenocarcinoma lung cancer cells and are synergistic when combined with traditional chemotherapy in apoptosis induction. Conclusions : The sensitivity of putative cancer stem cells to TRAIL-expressing MSCs, suggests their possible role in the prevention of cancer relapse. © 2010 Cancer Research UK.