CD163 Is Required for Protumoral Activation of Macrophages in Human and Murine Sarcoma.

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.

• Authors: Daisuke Shiraishi, Yukio Fujiwara, Hasita Horlad, Yoichi Saito, Toyohisa Iriki, Junko Tsuboki, Pan Cheng, Naomi Nakagata, Hiroshi Mizuta, Hirofumi Bekki, Yasuharu Nakashima, Yoshinao Oda, Motohiro Takeya, Yoshihiro Komohara
• Journal: Cancer research (Cancer Res) Vol. 78 Issue 12 Pg. 3255-3266 (06 15 2018) ISSN: 1538-7445 [Electronic] United States
• PMID: 29610117 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: ©2018 American Association for Cancer Research.

Chemical References

• Antigens, CD
• Antigens, Differentiation, Myelomonocytic
• CD163 antigen
• Receptors, Cell Surface

Topics

• Aged
• Animals
• Antigens, CD (genetics, immunology, metabolism)
• Antigens, Differentiation, Myelomonocytic (genetics, immunology, metabolism)
• Cell Line, Tumor (transplantation)
• Cell Proliferation
• Coculture Techniques
• Disease Models, Animal
• Disease Progression
• Female
• Humans
• Kaplan-Meier Estimate
• Macrophage Activation (immunology)
• Macrophages (immunology, metabolism)
• Male
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Middle Aged
• Neoplasm Grading
• Receptors, Cell Surface (genetics, immunology, metabolism)
• Sarcoma (immunology, mortality, pathology)
• Tumor Microenvironment (immunology)