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01-07-2010 | Original Article

Thrombin facilitates invasion of ovarian cancer along peritoneum by inducing monocyte differentiation toward tumor-associated macrophage-like cells

Authors: Ting Zhang, Zhengwen Ma, Ruili Wang, Ying Wang, Shujun Wang, Zhongping Cheng, Hong Xu, Xinjuan Jin, Weiping Li, Xipeng Wang

Published in: Cancer Immunology, Immunotherapy | Issue 7/2010

Abstract

Peritoneal metastasis is a distinct pathologic characteristic of advanced epithelial ovarian cancer (EOC), which is the most deadly disease of the female reproductive tract. The inflammatory environment of the peritoneum in EOC contains abundant macrophages, activated thrombin, and thrombin-associated receptors. However, little is known about the mechanism by which the thrombin–macrophages interaction contributes to tumor invasion and metastasis. We investigated the phenotype and cytokine/chemokine expression of thrombin-treated peripheral blood monocytes (MOs)/macrophages, it was found that the phenotype of MOs was altered toward a TAM-like macrophage CD163^highIL-10^highCCL18^highIL-8^high after thrombin stimulation. By Matrigel invasion assay, the conditioned medium of thrombin-stimulated MOs accelerated remarkable invasion of ES-2, SKOV3, and HO-8910, which was similar to invasive cell numbers of ascites stimuli (P < 0.05) and higher than MOs medium alone (P < 0.05). IL-8 was proposed as the major chemoattractant mediating EOC invasion based on MOs mRNA and protein expression profiling. It was observed that anti IL-8 monoclonal neutralizing antibody attenuated EOC cell invasion in a concentration-dependent manner. Increased transcriptional activation of NF-κB p50/p65 was identified in thrombin-treated MOs. This study provided insight the role of thrombin in the regulation of EOC peritoneal invasion via “educating” MOs.

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Title: Thrombin facilitates invasion of ovarian cancer along peritoneum by inducing monocyte differentiation toward tumor-associated macrophage-like cells
Authors: Ting Zhang
Zhengwen Ma
Ruili Wang
Ying Wang
Shujun Wang
Zhongping Cheng
Hong Xu
Xinjuan Jin
Weiping Li
Xipeng Wang
Publication date: 01-07-2010
Publisher: Springer-Verlag
Published in: Cancer Immunology, Immunotherapy / Issue 7/2010
Print ISSN: 0340-7004
Electronic ISSN: 1432-0851
DOI: https://doi.org/10.1007/s00262-010-0836-y

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