title: A Critical Role for CD200R Signaling in Limiting the Growth and Metastasis of CD200+ Melanoma.
abstract: CD200 is a cell surface glycoprotein that functions through engaging CD200R on cells of the myeloid lineage and inhibits their functions. Expression of CD200 was implicated in a variety of human cancer cells, including melanoma cells; however, its roles in tumor growth and immunity are not clearly understood. In this study, we used CD200R-deficient mice and the B16 tumor model to evaluate this issue. We found that CD200R-deficient mice exhibited accelerated growth of CD200(+), but not CD200(-), B16 tumors. Strikingly, CD200R-deficient mice receiving CD200(+) B16 cells i.v. exhibited massive tumor growth in multiple organs, including liver, lung, kidney, and peritoneal cavity, whereas the growth of the same tumors in wild-type mice was limited. CD200(+) tumors grown in CD200R-deficient mice contained higher numbers of CD11b(+)Ly6C(+) myeloid cells, exhibited increased expression of VEGF and HIF1α genes with increased angiogenesis, and showed significantly reduced infiltration of CD4(+) and CD8(+) T cells, presumably as the result of reduced expression of T cell chemokines, such as CXCL9 and CXCL16. The liver from CD200R-deficient mice, under metastatic growth of CD200(+) tumors, contained significantly increased numbers of CD11b(+)Gr1(-) myeloid cells and Foxp3(+) regulatory T cells and reduced numbers of NK cells. Liver T cells also had a reduced capacity to produce IFN-γ or TNF-α. Taken together, we revealed a critical role for CD200R signaling in limiting the growth and metastasis of CD200(+) tumors. Thus, targeting CD200R signaling may potentially interfere with the metastatic growth of CD200(+) tumors, like melanoma.
authors.affiliation: Department of Pathology and Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210;
authors.forename: Jin-Qing
authors.initials: JQ
authors.lastname: Liu
authors.affiliation: Department of Pathology and Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210;
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Talebian
authors.affiliation: Department of Pathology and Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210; Department of Gastroenterology, Guangdong Provincial Key Laboratory of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China;
authors.forename: Lisha
authors.initials: L
authors.lastname: Wu
authors.affiliation: Department of Pathology and Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210; Department of Gastroenterology, Guangdong Provincial Key Laboratory of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China;
authors.forename: Zhihao
authors.identifier: 0000-0001-5681-8459
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Gastroenterology, Guangdong Provincial Key Laboratory of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China;
authors.forename: Ming-Song
authors.initials: MS
authors.lastname: Li
authors.affiliation: Davis Medical Research Center, Columbus, OH 43210; and.
authors.forename: Laichu
authors.initials: L
authors.lastname: Wu
authors.affiliation: Pediatric Translational Medicine Institute, Shanghai Children's Medical Center, Shanghai Jiaotong University School of Medicine, Shanghai 200127, China.
authors.forename: Jianmin
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Department of Pathology and Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210;
authors.forename: Joseph
authors.identifier: 0000-0003-2490-5464
authors.initials: J
authors.lastname: Markowitz
authors.affiliation: Department of Pathology and Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210;
authors.forename: William E
authors.initials: WE
authors.lastname: Carson
authors.affiliation: Department of Pathology and Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210;
authors.forename: Sujit
authors.identifier: 0000-0002-8272-0807
authors.initials: S
authors.lastname: Basu
authors.affiliation: Department of Pathology and Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210; Pediatric Translational Medicine Institute, Shanghai Children's Medical Center, Shanghai Jiaotong University School of Medicine, Shanghai 200127, China Xue-Feng.Bai@osumc.edu.
authors.forename: Xue-Feng
authors.initials: XF
authors.lastname: Bai
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000276:immunology / Q000378:metabolism*; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D055786:Gene Knockout Techniques; D006801:Humans; D007150:Immunohistochemistry; D016246:Lymphocytes, Tumor-Infiltrating / Q000473:pathology; D008546:Melanoma, Experimental / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009361:Neoplasm Invasiveness / Q000276:immunology / Q000473:pathology*; D009389:Neovascularization, Pathologic / Q000276:immunology / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology*; D059016:Tumor Microenvironment / Q000502:physiology
chemical_list: D015703:Antigens, CD; C042739:antigens, CD200