| 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
|
| リソース情報 |
| ヒト・動物細胞 |
NMFH-1(RCB2346)
LM8(RCB1450) |
