論文 - 詳細
| RRC ID | 66955 |
|---|---|
| 著者 | 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. |
| タイトル | CD163 Is Required for Protumoral Activation of Macrophages in Human and Murine Sarcoma. |
| ジャーナル | 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. |
| 巻・号 | 78(12) |
| ページ | 3255-3266 |
| 公開日 | 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 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
|
| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 3 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | NMFH-1(RCB2346) LM8(RCB1450) |