Centre For Respiratory Research, Rayne Institute, University College London, 5 University Street, London WC1E 6JJ, UK.
Br J Cancer. 2010 Nov 23;103(11):1692-7. doi: 10.1038/sj.bjc.6605952. Epub 2010 Nov 9.
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.
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.
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.
The sensitivity of putative cancer stem cells to TRAIL-expressing MSCs, suggests their possible role in the prevention of cancer relapse.
肿瘤中含有具有干细胞样特性的侧群（SP）细胞，这些细胞具有更高的肿瘤形成能力、对传统疗法的抗性，并且可能是导致患者治疗失败和复发的原因。
我们设计了表达凋亡配体 TNF 相关凋亡诱导配体（TRAIL）的间充质干细胞（MSCs）。通过 Hoechst 流式细胞术将鳞状细胞（H357）和肺（A549）癌细胞系分选为侧群（SP）和非侧群（非-SP）。通过流式细胞术和集落形成能力评估了 SP 和非-SP 癌细胞群与表达 TRAIL 的 MSCs 以及米托蒽醌化疗的共同作用下的生存和生长情况。
表达 TRAIL 的间充质干细胞向肿瘤迁移，并减少原发性癌症和转移灶的生长。本报告表明，这些细胞可以诱导鳞状细胞癌和肺腺癌的 SP 细胞发生凋亡、死亡和集落形成减少，并且与传统化疗联合使用时具有协同诱导凋亡的作用。
TRAIL 表达 MSC 对疑似癌症干细胞的敏感性表明，它们可能在预防癌症复发方面发挥作用。
