With Clec - 1 In The Study Of The Role Of The Microglia Activation With Clec - 1 And Promote The Progress Of Breast Cancer Research

Part I Study on the role of CLEC-1in microglia activationThe excessive activation of microglia, which believed destroying the homeostatic environment and leading to the immune imbalance of central nervous system (CNS), has long been regarded as a crucial mechanism in almost all of the CNS diseases.C-type lectin-like receptor-1(CLEC-1), encoded by the natural killer gene complex (NKC), has recently been reported modulating Th17differentiation and regulating the immune responses in a model of rat allograft tolerance.In the present study, we detected a prominent expression of CLEC-1in microglia cells in CNS and a dynamic expression pattern of CLEC-1after inflammatory factor LPS-induced microglia activation. With regard to the LPS-induced inflammatory cytokines secretion, no significant difference was found between the CLEC-1down-and up-expression groups. However, following the treatment of IL-10, a well-known negative-immunoregulator, CLEC-1mRNA level showed an obvious growth. And the LPS-evoked TLR4activation in microglia cells was partly abolished by CLEC-1over-expression, suggesting CLEC-1might serve as a down regulator of IL-10and affect the microglia activation through a cross-talk with TLR4signaling. More interestingly, TUNEL assay and Western-blot results demonstrated that CLEC-1over-expression may promote microglia apoptosis. Taken together, CLEC-1may affect the pro-inflammatory factor induced microglia activation through its cross-talk with TLR4and a pro-apoptotic mechanism.CLEC-1could be a useful target to modulate the disordered immune responses in CNS diseases Part Ⅱ Study of the regulation role of CLEC-1in breast cancer progressionThe incidence and metastasis of breast cancer is a multi-step, multi-link, multi-factors involved complex process, and the cross talk between cancer cell contributes to an inflammatory or negative-immune-microenvironment which play an important role in tumor progression. CLEC-1, a member of the C-type-lectin-like receptor family, has been reported to inhibit the Th17differentiation of allogeneic T cells in rat dendritic cells and increase the regulatory Foxp3+T cells poll, suggesting the negative role of CLEC-1in immune-regulation. But its role in tumorigenesis have not been reported so far.Here, we revealed that CLEC-1was highly expressed in human breast cancer tissue. Its expression positively correlated with tumor grade, tumor volume and lymph node status. Consistent with these observations, CLEC-1promoted colony formation, invasion rather than proliferation and migration in breast cancer cell line MCF-7and MDA-MB-231. It has been well documented that MMPs are essential for tumor invasion in breast cancer. In the present investigation, we demonstrated that TGF-β upregulated CLEC-1expression. Furthermore, our data also showed that CLEC-1upregulated MMP9expression, indicating a possible role of CLEC-1in TGF-β-MMP9induced cell invasion..Taken together, our studies suggest that CLEC-1might promote tumor formation and invasion. Over expression of CLEC-1may contribute to breast cancer development and progression in TGF-β-MMP9dependent cell signaling.