The effects of human mesenchymal stem cells on the proliferative, migratory, and invasive properties of Glioblastoma multiforme

Glioblastoma Multiforme (GBM) is the most common and aggressive brain tumor. GBM rapidly invades the surrounding brain tissue and resists most chemotherapeutic agents resulting in a high mortality rate even after receiving treatment. Previous studies suggest that several cancer stromal cells, especially the human mesenchymal stem cells (hMSCs), which are parts of the tumor, play essential roles in the growth, metastasis, and drug responses of GBM cells. However, distinct sources of hMSCs might release different combinations of soluble factors that affect GBM cells differently. Therefore, in the present study, we established hMSCs from the placenta (PL-hMSCs) and chorion (CH-hMSCs) to study the effects of their released soluble factors on the proliferation, migration, and invasion of human GBM cells, U251-MG. The results showed that the soluble factors derived from PL-hMSCs suppressed the proliferation of U251 cells in a dose-dependent manner, while most CH-hMSCs did not have such an effect. Moreover, the soluble factors derived from PL-hMSCs have a cytoprotective effect on U251-MG cells, while CH-hMSC-derive soluble factors did not. On the contrary, the soluble factors derived from both hMSC sources increased the migration of U251-MG cells but did not affect the invasive property of those cells. The gene expression analysis showed that the soluble factors derived from PL-hMSCs and CH-hMSCs down-regulated the expression levels of E2F1, E2F2, NFKB1, NFKB2, NOTCH1, NOTCH2, PROM1, MYC, and ITGA1 genes which promote proliferation and stemness of hGBM. These results suggest that the soluble factors derived from PL-hMSCs might suppress the proliferation of GBM cells by inhibiting the expression of genes that promote GBM proliferation. The functional study indicates that the suppressive effect of PL-hMSCs on U251 cell proliferation was mediated, at least in part, through TGF-β activators and Wnt inhibitors rather than NF-KB signaling. Our study provides a better understanding of the interaction between the GBM cells and hMSCs, which are the critical parts of the GBM stroma. This knowledge could be used to develop a more effective treatment that improves the survival and quality of life of GBM patients.