Tumor-associated macrophages promote invasion via Toll-like receptors signaling in patients with ovarian cancer

Abstract

Tumor-associated macrophages (TAMs) derived from peripheral blood monocytes recruit into tumor microenvironment and display functions associated with tumor progression. The mechanisms by which TAMs display roles that associated with the invasion ability of ovarian cancer have not been well investigated. In our research, we found abundant TAMs infiltrate in ovarian cancer compared with benign ovarian tumor tissues. Levels of matrix metalloproteinase (MMP)-2, MMP-9 and MMP-10, and Toll-like receptors (TLRs) signaling proteins were evaluated in ovarian cancer. The high level of TAMs was associated with metastasis and advance of patients with ovarian cancer. TAMs and ovarian cancer cell line SKOV3 were cocultured in vitro, MMPs level and the invasion ability of SKOV3 cells were significantly up-regulated. The coculture process was correlated with the activation of TLRs signaling and downstream nuclear factor (NF)-κB p65 and microtubule-associated proteins (MAPs) kinases pathway in SKOV3. In addition, pre-incubation with TLRs signaling inhibitors remarkably suppressed invasion ability of SKOV3. Levels of TLRs signaling pathways proteins were also down-regulated in this blocking process. These findings demonstrated that TAMs promoted up-regulation of MMP-2, MMP-9 and MMP-10 expressions and enhanced ovarian cancer cells invasion via TLRs signaling pathway. We conclude that TAMs could enhance ovarian cancer cells invasion and ultimately promote ovarian cancer progression.

Keywords: Epithelial ovarian cancer; Matrix metalloproteinases; Toll-like receptors; Tumor-associated macrophages.