RRC ID 66955
Author Shiraishi D, Fujiwara Y, Horlad H, Saito Y, Iriki T, Tsuboki J, Cheng P, Nakagata N, Mizuta H, Bekki H, Nakashima Y, Oda Y, Takeya M, Komohara Y.
Title CD163 Is Required for Protumoral Activation of Macrophages in Human and Murine Sarcoma.
Journal Cancer Res
Abstract Recent findings have shown the significance of CD163-positive macrophages in tumor progression, yet there have been few studies on the function of CD163 in macrophages. Here, we uncover the role of CD163 in macrophage activation using CD163-deficient mice and human samples. We detected CD163 in 62 undifferentiated pleomorphic sarcoma samples, in which a high percentage of CD163-positive macrophages was associated with decreased overall survival and higher histologic grade. We observed macrophage-induced tumor cell proliferation in cocultures of human monocyte-derived macrophages and leiomyosarcoma (TYLMS-1) and myxofibrosarcoma (NMFH-1) cell lines, which was abrogated by silencing of CD163. Tumor development of sarcoma (MCA205 and LM8) cells in CD163-deficient mice was significantly abrogated in comparison with wild-type (WT) mice. Coculture with WT peritoneal macrophages significantly increased proliferation of MCA205 cells but decreased in the presence of CD163-deficient macrophages. Production of IL6 and CXCL2 in CD163-deficient macrophages was suppressed in comparison with WT macrophages, and overexpression of CD163 in CD163-deficient macrophages induced production of IL6 and CXCL2. Silencing of IL6 but not CXCL2 abrogated macrophage-induced proliferation of MCA205 cells. Taken together, our results show that CD163 is involved in protumoral activation of macrophages and subsequent development and progression of tumors in mice and humans.Significance: Macrophage CD163-mediated induction of IL6 promotes tumor development and progression in murine and human malignant tumors. Cancer Res; 78(12); 3255-66. ©2018 AACR.
Volume 78(12)
Pages 3255-3266
Published 2018-6-15
DOI 10.1158/0008-5472.CAN-17-2011
PII 0008-5472.CAN-17-2011
PMID 29610117
MeSH Aged Animals Antigens, CD / genetics Antigens, CD / immunology Antigens, CD / metabolism* Antigens, Differentiation, Myelomonocytic / genetics Antigens, Differentiation, Myelomonocytic / immunology Antigens, Differentiation, Myelomonocytic / metabolism* Cell Line, Tumor / transplantation Cell Proliferation Coculture Techniques Disease Models, Animal Disease Progression Female Humans Kaplan-Meier Estimate Macrophage Activation / immunology* Macrophages / immunology* Macrophages / metabolism Male Mice Mice, Inbred C57BL Mice, Knockout Middle Aged Neoplasm Grading Receptors, Cell Surface / genetics Receptors, Cell Surface / immunology Receptors, Cell Surface / metabolism* Sarcoma / immunology* Sarcoma / mortality Sarcoma / pathology Tumor Microenvironment / immunology*
IF 9.727
Human and Animal Cells NMFH-1(RCB2346) LM8(RCB1450)