title: CD11b deficiency suppresses intestinal tumor growth by reducing myeloid cell recruitment.
abstract: 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 Apc(Min/+) 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.
authors.affiliation: Vascular Biology Research Institute, School of Basic Course, Guangdong Pharmaceutical University, Guangzhou 510006, China.
authors.forename: Qian-Qian
authors.initials: QQ
authors.lastname: Zhang
authors.affiliation: Vascular Biology Research Institute, School of Basic Course, Guangdong Pharmaceutical University, Guangzhou 510006, China.
authors.forename: Xi-Wen
authors.initials: XW
authors.lastname: Hu
authors.affiliation: Vascular Biology Research Institute, School of Basic Course, Guangdong Pharmaceutical University, Guangzhou 510006, China.
authors.forename: Yi-Long
authors.initials: YL
authors.lastname: Liu
authors.affiliation: Vascular Biology Research Institute, School of Basic Course, Guangdong Pharmaceutical University, Guangzhou 510006, China.
authors.forename: Zhi-Jin
authors.initials: ZJ
authors.lastname: Ye
authors.affiliation: Vascular Biology Research Institute, School of Basic Course, Guangdong Pharmaceutical University, Guangzhou 510006, China.
authors.forename: Yi-He
authors.initials: YH
authors.lastname: Gui
authors.affiliation: Vascular Biology Research Institute, School of Basic Course, Guangdong Pharmaceutical University, Guangzhou 510006, China.
authors.forename: Da-Lei
authors.initials: DL
authors.lastname: Zhou
authors.affiliation: Vascular Biology Research Institute, School of Basic Course, Guangdong Pharmaceutical University, Guangzhou 510006, China.
authors.forename: Cui-Ling
authors.initials: CL
authors.lastname: Qi
authors.affiliation: Vascular Biology Research Institute, School of Basic Course, Guangdong Pharmaceutical University, Guangzhou 510006, China.
authors.forename: Xiao-Dong
authors.initials: XD
authors.lastname: He
authors.affiliation: Institute of Immunology, Institute of Medical Sciences, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
authors.forename: Honglin
authors.initials: H
authors.lastname: Wang
authors.affiliation: Vascular Biology Research Institute, School of Basic Course, Guangdong Pharmaceutical University, Guangzhou 510006, China.
authors.forename: Li-Jing
authors.initials: LJ
authors.lastname: Wang
mesh_terms: D025601:Adenomatous Polyposis Coli Protein / Q000172:deficiency / Q000235:genetics; D000818:Animals; D039481:CD11b Antigen / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D002478:Cells, Cultured; D054370:Chemokine CXCL9 / Q000096:biosynthesis / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D045325:HCT116 Cells; D006801:Humans; D015151:Immunoblotting; D007371:Interferon-gamma / Q000096:biosynthesis / Q000235:genetics; D007414:Intestinal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D022423:Myeloid Cells / Q000378:metabolism* / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D047368:Tumor Burden / Q000235:genetics*; D059016:Tumor Microenvironment / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: D025601:Adenomatous Polyposis Coli Protein; D039481:CD11b Antigen; D054370:Chemokine CXCL9; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma