CD163 is required for protumoral activation of macrophages in human and murine sarcoma

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 histological grade. We observed macrophage-induced tumor cell proliferation in co-cultures 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 to WT mice. Co-culture with WT peritoneal macrophages significantly increased proliferation of MCA205 cells but decreased in the presence of CD163-deficient macrophages. Production of IL-6 and CXCL2 in CD163-deficient macrophages was suppressed in comparison to WT macrophages, and overexpression of CD163 in CD163-deficient macrophages induced production of IL-6 and CXCL2. Silencing of IL-6 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.

from Cancer via ola Kala on Inoreader https://ift.tt/2Efge0h
via IFTTT