Immunosuppressive effect of bone marrow-derived mesenchymal stem cells in inflammatory microenvironment favours the growth of B16 melanoma cells.
Bottom Line: We first compared the promotive capacity of bone marrow-derived MSCs on B16 melanoma cells growth in vivo, pre-incubated or not with the inflammatory cytokines interferon (IFN)-γ and tumour necrosis factor (TNF)-α.These cytokine combinations provoke the expression of inducible nitric oxide synthase (iNOS) by MSCs.The impulsive effect of MSCs treated with inflammatory cytokines on B16 melanoma cells in vivo can be reversed by inhibitor or short interfering RNA of iNOS.
Affiliation: Tumor Immunology and Gene Therapy Center, Eastern Hepatobiliary Surgery Hospital, The Second Military Medicial University, Shanghai, China.Show MeSH
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Mentions: We implanted B16 melanoma cells in Balb/c mice with MSCs, which were pre-incubated or not with the inflammatory cytokines, to test the immunosuppression properties of MSCs that favour the B16 melanoma cells escaping from the rejection of Balb/c mice. While B16 melanoma cells developed into tumours rapidly after implanted subcutaneously in C57BL/6 mice, they were fully rejected in Balb/c mice, indicating no tumour formation at all. Once we implanted B16 melanoma cells mixed with MSCs in Balb/c mice, the incidence of tumour increased. Moreover, the tumour incidence could increase higher if the MSCs were pretreated with proinflammatory cytokines before they were mixed with B16 cells (Fig. 2A). These results indicate that MSCs have the ability to assist the B16 cells escaping from immune surveillance and this capacity is induced by proinflammatory cytokines.
Affiliation: Tumor Immunology and Gene Therapy Center, Eastern Hepatobiliary Surgery Hospital, The Second Military Medicial University, Shanghai, China.