TRAIL-expressing mesenchymal stem cells kill the putative cancer stem cell population.
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.
Centre For Respiratory Research, Rayne Institute, University College London, 5 University Street, London WC1E 6JJ, UK.
M R
MR
Loebinger
E K
EK
Sage
D
D
Davies
S M
SM
Janes
D000230:Adenocarcinoma / Q000473:pathology / Q000628:therapy; D000328:Adult; D017209:Apoptosis; D045744:Cell Line, Tumor; D018920:Coculture Techniques; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology / Q000628:therapy; D059630:Mesenchymal Stem Cells / Q000502:physiology*; D008942:Mitoxantrone / Q000494:pharmacology; D014411:Neoplastic Stem Cells / Q000473:pathology*; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000502:physiology*
D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; D008942:Mitoxantrone