Tumor-associated macrophages promote invasion via Toll-like receptors signaling in patients with ovarian cancer.
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.
Department of Laboratory Medicine, the First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China; National Key Clinical Department of Laboratory Medicine, Nanjing 210029, China.
Xing
X
Ke
Department of Laboratory Medicine, Nanjing Children's Hospital Affiliated to Nanjing Medical University, 210029 Nanjing, China.
Shuping
S
Zhang
Department of Laboratory Medicine, the First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China; National Key Clinical Department of Laboratory Medicine, Nanjing 210029, China.
Meng
M
Wu
Department of Laboratory Medicine, the First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China; National Key Clinical Department of Laboratory Medicine, Nanjing 210029, China.
Jianfang
J
Lou
Department of Laboratory Medicine, the First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China; National Key Clinical Department of Laboratory Medicine, Nanjing 210029, China.
Jiexin
J
Zhang
Department of Laboratory Medicine, the First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China; National Key Clinical Department of Laboratory Medicine, Nanjing 210029, China.
Ting
T
Xu
Department of Laboratory Medicine, the First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China; National Key Clinical Department of Laboratory Medicine, Nanjing 210029, China.
Lei
L
Huang
Department of Laboratory Medicine, the First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China; National Key Clinical Department of Laboratory Medicine, Nanjing 210029, China.
Peijun
P
Huang
Department of Laboratory Medicine, the First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China; National Key Clinical Department of Laboratory Medicine, Nanjing 210029, China. Electronic address: wangfang@njmu.edu.cn.
Fang
F
Wang
Department of Laboratory Medicine, the First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China; National Key Clinical Department of Laboratory Medicine, Nanjing 210029, China. Electronic address: sypan@njmu.edu.cn.
Shiyang
S
Pan
D045744:Cell Line, Tumor; D018920:Coculture Techniques; D005260:Female; D006801:Humans; D008264:Macrophages / Q000378:metabolism*; D053506:Matrix Metalloproteinase 10 / Q000235:genetics / Q000378:metabolism*; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000378:metabolism*; D051193:Toll-Like Receptors / Q000235:genetics / Q000378:metabolism*
D051193:Toll-Like Receptors; C511770:MMP10 protein, human; D053506:Matrix Metalloproteinase 10; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9
Epithelial ovarian cancer; Matrix metalloproteinases; Toll-like receptors; Tumor-associated macrophages