IFN-?-secreting-mesenchymal stem cells exert an antitumor effect in vivo via the TRAIL pathway.

ABSTRACT: Mesenchymal stem cells (MSCs) can exhibit either prooncogenic or antitumor properties depending on the context. Based on our previous study, we hypothesized that MSCs engineered to deliver IFN-? would kill cancer cells through persistent activation of the TRAIL pathway. Human bone-marrow (BM-) derived MSCs were isolated, amplified, and transduced with a lentiviral vector encoding the IFN-? gene under the control of the EF1? promoter. The IFN-?-modified MSCs effectively secreted functional IFN-?, which led to long-term expression of TRAIL. More importantly, the IFN-?-modified MSCs selectively induced apoptosis in lung tumor cells through caspase-3 activation within the target cells. The percentage of activated-caspase-3-positive tumor cells in IFN-?-modified MSCs cocultures was significantly higher than in control MSCs cocultures. Treatment with anti-TRAIL antibody dramatically suppressed the caspase-3 activation observed in H460 cells. After injection into nude mice, the IFN-?-modified MSCs inhibited the growth and progression of lung carcinoma compared with control cells. Collectively, our results provide a new strategy for tumor therapy that utilizes IFN-?-modified MSCs.

SUBMITTER: Yang X 

PROVIDER: S-EPMC4058226 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature