CD11b deficiency suppresses intestinal tumor growth by reducing myeloid cell recruitment.
CD11b deficiency suppresses intestinal tumor growth by reducing myeloid cell recruitment.
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CD11b 缺陷通过减少骨髓细胞募集来抑制肠道肿瘤生长
DOI：
10.1038/srep15948
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发表时间：
2015-11-03
影响因子：
4.6
通讯作者：
Wang LJ
中科院分区：
文献类型：
--
作者：
Zhang QQ;Hu XW;Liu YL;Ye ZJ;Gui YH;Zhou DL;Qi CL;He XD;Wang H;Wang LJ
Mac-1（CD 11b）在骨髓来源的免疫细胞上表达。CD 11b与配体结合以调节白细胞粘附和穿过内皮或上皮的迁移。在此，我们采用CD 11b基因敲除小鼠和ApcMin/+自发性肠腺瘤小鼠模型来阐明CD 11b在肠肿瘤发生中的功能。我们发现，CD 11b缺陷可能有助于抑制髓系细胞向肿瘤微环境的运输，并灭活Wnt/β-catenin通路以抑制肿瘤生长。这种作用部分是通过抑制髓系细胞介导的TNF-α分泌减少介导的，这抑制了髓系来源的抑制细胞向肿瘤微环境的募集，随后诱导IFN-γ和CXCL 9的产生。这项工作为CD 11b可能作为重要癌基因发挥作用的机制提供了证据，并强调了CD 11b作为CRC治疗靶点的潜力。
Mac-1 (CD11b) is expressed on bone marrow-derived immune cells. CD11b binds to ligands to regulate leukocyte adhesion and migration across the endothelium or epithelium. Here, we employed CD11b knockout mice and an ApcMin/+ spontaneous intestinal adenoma mouse model to clarify the function of CD11b in intestinal tumorigenesis. We showed that CD11b deficiency may contribute to the inhibition of myeloid cell trafficking to the tumor microenvironment and inactivated Wnt/β-catenin pathway to suppress tumor growth. This effect was partly mediated by inhibiting the myeloid cell-mediated decrease in TNF-α secretion, which inhibits the recruitment of myeloid-derived suppressor cells to the tumor microenvironment and subsequently induces IFN-γ and CXCL9 production. This work provides evidence for the mechanism by which CD11b may function as an important oncogene and highlights the potential of CD11b as a therapeutic target in CRC.