Tumor-Associated Macrophages Recruit CCR6 Regulatory T Cells and Promote the Development of Colorectal Cancer via Enhancing CCL20 Production in MiceReport as inadecuate




Tumor-Associated Macrophages Recruit CCR6 Regulatory T Cells and Promote the Development of Colorectal Cancer via Enhancing CCL20 Production in Mice - Download this document for free, or read online. Document in PDF available to download.

Background

Tumor-associated macrophages TAMs remodel the colorectal cancer CRC microenvironment. Yet, findings on the role of TAMs in CRC seem to be contradictory compared with other cancers. FoxP3+ regulatory T Treg-cells dominantly infiltrate CRC. However, the underlying molecular mechanism in which TAMs may contribute to the trafficking of Treg-cells to the tumor mass remains unknown.

Methodology-Principal Findings

CRC was either induced by N-methyl-N-nitrosourea MNU and H. pylori or established by subcutaneous injection of mouse colorectal tumor cell line CMT93 in mice. CMT93 cells were co-cultured with primary macrophages in a transwell apparatus. Recruitment of FoxP3 green fluorescence protein positive FoxP3GFP+ Treg-cells was assessed using the IVIS Imaging System or immunofluorescence staining. A role for macrophages in trafficking of Treg-cells and in the development of CRC was investigated in CD11b diphtheria toxin receptor CD11b-DTR transgenic C57BL-6J mice in which macrophages can be selectively depleted. Treg-cells remarkably infiltrated solid tumor, and predominantly expressed the homing chemokine receptor CCR 6 in the induced CRC model. Both CMT93 cancer cells and macrophages produced a large amount of CCL20, the sole ligand of CCR6 in vitro and in vivo. Injection of recombinant mouse CCL20 into tumor sites promoted its development with a marked recruitment of Treg-cells in the graft CRC model. Conditional macrophage ablation decreased CCL20 levels, blocked Treg-cell recruitment and inhibited tumor growth in CD11b-DTR mice grafted with CMT93.

Conclusions-Significance

TAMs recruit CCR6+ Treg-cells to tumor mass and promote its development via enhancing the production of CCL20 in a CRC mouse model.



Author: Jinlin Liu , Ning Zhang , Qun Li, Weiwei Zhang, Fang Ke, Qibin Leng, Hong Wang, Jinfei Chen, Honglin Wang

Source: http://plos.srce.hr/



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