Open AccessImmunosuppressive effect of bone marrow‐derived mesenchymal stem cells in inflammatory microenvironment favours the growth of B16 melanoma cells
Author(s) -
Han Zhipeng,
Tian Zhiqiang,
Lv Gang,
Zhang Li,
Jiang Guocheng,
Sun Kai,
Wang Chenyang,
Bu Xinxin,
Li Rong,
Shi Yufang,
Wu Mengchao,
Wei Lixin
Publication year - 2011
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/j.1582-4934.2010.01215.x
Subject(s) - mesenchymal stem cell , melanoma , in vivo , bone marrow , cancer research , cytokine , tumor necrosis factor alpha , immunology , immunotherapy , tumor microenvironment , immune system , stem cell , medicine , biology , pathology , microbiology and biotechnology
Mesenchymal stem cells (MSCs) are studied for their potential clinical use in regenerative medicine, tissue engineering and tumour therapy. However, the therapeutic application of MSCs in tumour therapy still remains limited unless the immunosuppressive role of MSCs for tumour growth in vivo is better understood. In this study, we investigated the mechanism of MSCs favouring tumour escape from immunologic surveillance in inflammatory microenvironment. 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. We showed that the development of B16 melanoma cells is faster when co‐injected with MSCs pre‐incubated with IFN‐γ and TNF‐α compared with control groups. Moreover, tumour incidence increases obviously in allogeneic recipients when B16 melanoma cells were co‐injected with MSCs pre‐incubated with IFN‐γ and TNF‐α. We then demonstrated that the immunosuppressive function of MSCs was elicited by IFN‐γ and 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. Our results suggest that the MSCs in tumour inflammatory microenvironment may be elicited of immunosuppressive function, which will help tumour to escape from the immunity surveillance.