Studies have demonstrated that mesenchymal stem cells (MSCs) can promote tumor growth, and MSC microvesicles (MVs) are very important in the tumor microenvironment and information transfer between cells during tumorigenesis and development. However, the potential effects and mechanisms of MSC-MVs on tumor growth are still controversial. Here in this study, we investigated the roles and effects of human bone marrow MSC-MVs (hBMSC-MVs) on human osteosarcoma (U2OS) cell growth under hypoxia in vitro and in vivo. BMSC-MVs were harvested and purified by ultracentrifugation. U2OS cells were treated with different concentrations of hBMSC-MVs under hypoxia. Cell viability and migration was measured by MTT test, transwell invasion assay and scratch migration assay. The expression of the signaling molecules of AKT, VEGF, GLUT1 and Bax, cleaved-caspase3 in U2OS cells cultured with MVs under hypoxia was determined by western blot. U2OS/siHIF-1α or U2OS/NC cells mixed with/without MVs were subcutaneously injected into nude mice; the tumor size and weight were detected. We found that hBMSC-MVs promoted U2OS cell proliferation and migration under hypoxia in vitro, and that was partially associated with the PI3K/AKT and HIF-1α pathways. MVs co-injected with U2OS cells promoted tumor growth in a mouse xenograft model. siHIF-1α transfection reversed these changes to some extent. The function of hBMSC-MVs on U2OS cell progression and tumor growth was associated with PI3K/AKT and HIF-1α pathway under hypoxia. These findings support a new mechanism suggesting the contribution of MSC-MVs to tumor growth.
Keywords: HIF-1α; Hypoxia; Microvesicles; Osteosarcoma; PI3K/AKT.