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In cancer treatment, the most attractive feature of mesenchymal stem cells (MSCs) is it's homing to tumor tissues. MSC is an important part of the “colon cancer stem cell niche”, but little research has been done on the tropism of human MSCs toward colon cancer stem cells (CCSCs). In this study, we first compared the effects of three tissue‐derived MSCs (bone marrow, adipose tissue, and placenta) in vivo on colon tumor xenograft growth. Then, we analyzed the tropism of bone marrow‐derived MSCs (BMSCs) toward normal intestinal epithelial cells (NCM460), parental colon cancer cells, CD133−/CD44−, and CD133+/CD44+ colon cancer cells in vitro. Microarray analysis and in vitro experiments explored the mechanism of mediating the homing of BMSCs toward CCSCs. Compared with the parental and CD133−/CD44− colon cancer cells, CD133+/CD44+ cells have a stronger ability to recruit BMSCs. In addition, BMSCs were significantly transformed into cancer‐associated fibroblasts after being recruited by CCSCs. After coculture of BMSCs and CCSCs, the expression of interleukin (IL)‐6, IL‐8, IL‐32, and CCL20 was significantly increased. Compared with parental strains, CD133−/CD44− cells, and NCM460, BMSC secreted significantly more IL‐8 after coculture with CD133+/CD44+ cells. Low concentration of IL‐8 peptide inhibitors (100 ng/ml) and CXC receptor 2 (CXCR2) inhibitors have little effect on the migration of BMSCs, but can effectively weaken CCSC stemness and promote dormant CSCs in the coculture system to re‐enter into the cell cycle. The endogenous IL‐8 knockout in BMSCs or BMSCs loaded with IL‐8 and/or CXCR2 inhibitors will make the therapy of BMSC targeting CCSCs function at its best.

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Background/Aims: The aim of this study was to investigate the involvement of inducible co-stimulatory ligand (ICOSL) expression in stimulation of mast cells (MCs) by TNF-α and the ability of TNF-α stimulation of MCs to influence CD4+ T cell differentiation and function. The mechanisms underlying TNF-α stimulation of MCs were also explored. Methods: Mast cells and CD4⁺ T cells were prepared from C57BL/6 mice (aged 6–8 weeks). ICOSL expression by MCs was measured by real-time PCR and flow cytometry, and levels of IL-4, IL-10 and IFN-γ were measured by ELISA. Results: ICOSL expression by MCs was increased by TNF-α stimulation, and resulted in interaction with CD4+ T cells. The IL-4 and IL-10 levels in the co-culture system increased, while IFN-γ levels decreased. Furthermore, CD4+CD25+Foxp3+ T cell proliferation was induced by co-culture with TNF-α-stimulated MCs. The mechanism by which TNF-α stimulated MCs was dependent on the activation of the MAPK signaling pathway. Conclusion: TNF-α upregulated the expression of ICOSL on mast cells via a mechanism that is dependent on MAPK phosphorylation. TNF-α-treated MCs promoted the differentiation of regulatory T cells and induced a shift in cytokine expression from a Th1 to a Th2 profile by up-regulation ICOSL expression and inhibition of MC degranulation. Our study reveals a novel mechanism by which mast cells regulate T cell function.