期刊
EXPERIMENTAL CELL RESEARCH
卷 313, 期 4, 页码 677-687出版社
ELSEVIER INC
DOI: 10.1016/j.yexcr.2006.11.019
关键词
activated protein C; EPCR; PAR-1; migration; transwell invasion and chemotaxis assay; Na butyrate; hirudin
资金
- NHLBI NIH HHS [T32 HL69768, T32 HL069768, R01 HL032656, HL-32656] Funding Source: Medline
- NINDS NIH HHS [F31 NS054590, F31 NS054590-01A1] Funding Source: Medline
Activated protein C (APC) is a serine protease that regulates thrombin (IIa) production through inactivation of blood coagulation factors Va and VIIIa. APC also has non-hemostatic functions related to inflammation, proliferation, and apoptosis through various mechanisms. Using two breast cancer cell lines, MDA-MB-231 and MDA-MB-435, we investigated the role of APC in cell chemotaxis and invasion. Treatment of cells with increasing APC concentrations (1-50 mu g,/ml) increased invasion and chemotaxis in a concentration-dependent manner. only the active form of APC increased invasion and chemotaxis of the MDA-MB-231 cells when compared to 3 inactive APC derivatives. Using a modified checkerboard analysis, APC was shown to only affect migration when plated with the cells; therefore, APC is not a chemoattractant. Blocking antibodies to endothelial protein C receptor (EPCR) and protease-activated receptor-1 (PAR-1) attenuated the effects of APC on chemotaxis in the MDA-MB-231 cells. Finally, treatment of the MDA-MB-231 cells with the proliferation inhibitor, Na butyrate, showed that APC did not increase migration by increasing cell number. Therefore, APC increases invasion and chemotaxis of cells by binding to the cell surface and activating specific signaling pathways through EPCR and PAR-1. (c) 2006 Elsevier Inc. All rights reserved.
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