The role of PTEN in human bone marrow-derived mesenchymal stem cells mediated tumor cells suppression.

Abstract

Human bone marrow-derived mesenchymal stem cells (MSC) have been increasingly used as a vehicle for gene delivery to cancer. Still, little is known about the role of MSC in the tumor microenvironment. Our laboratory has previously observed tumor suppression in glioma-bearing mice co-injected with human bone marrow-derived mesenchymal stem cells. However, this effect was not observed with PTEN deficient glioma cells. In present study, we employed shRNA as a mean to silence PTEN gene expression (loss-of-function assay). With the observed 26.2% of cell enhancement in MSC/ ∆Gli36-shPTEN co-culture, findings from the loss- of- function assay had indicated that expression of PTEN could be correlated with MSC-mediated suppression. In parallel, isogenic glioma cell lines U251, which overexpresses wild-type PTEN upon tetracycline treatment, resulted in 1.43-fold glioma cell growth retardation when cultured in the presence of MSC. These gain-of-function experiments were in line with the findings in the loss-of-function experiments. In summary, our results had demonstrated the importance of functional PTEN expression in relation to the MSC-mediated tumor cells suppression.