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.
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The authors thank professor Guo for his technical support and critical discussions.
Compliance with ethical standards
All experimental procedures were approved by the Medical Ethical Committee of the Sun Yat-sen University and the Ethical Commission Academy of Military Medicine Science, both of which approved the use of mice for this study (D11-2050 and D11-1004) [SCXK(Jing) 2012-0001]. All applicable international, national, and institutional guidelines for the care and use of animals were followed.
Research involving human and/or animal participants
All procedures performed in studies involving human participants were in accordance with the ethical standards of the Institutional Medical Research Ethics Committee of the First Affiliated Hospital of Sun Yat-sen University, and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
Informed consent was obtained from all individual participants included in the study.
Conflict of interest
All the authors confirm that no financial or non-financial conflict of interests exists.
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