Journal
EXPERIMENTAL CELL RESEARCH
Volume 316, Issue 3, Pages 314-328Publisher
ELSEVIER INC
DOI: 10.1016/j.yexcr.2009.10.024
Keywords
Activated Protein C; EPCR; PAR-1; EGFR; migration-invasion; angiogenesis; aortic rings
Categories
Funding
- National Institutes of Health [F31 NS054590, T32 HL697668, R01 HL32656]
- Thomas and Carolyn Royster Fellowship
- Robert H. Wagner Scholarship
- Susan G. Komen Breast Cancer Foundation [BCTR0503475, BCTR45206]
Ask authors/readers for more resources
Activated protein C (APC), an anticoagulant serine protease, has been shown to have non-hemostatic functions related to inflammation, cell survival, and cell migration. In this study we investigate the mechanism by which APC promotes angiogenesis and breast cancer invasion using ex vivo and in vitro methods. When proteolytically active, APC promotes cell motility/invasion and tube formation of endothelial cells. Ex vivo aortic ring assays verify the role of APC in promoting angiogenesis, which was determined to be dependent on EGFR and MMP activation. Given the capacity of APC to promote angiogenesis and the importance of this process in cancer pathology, we investigated whether the mechanisms by which APC promotes angiogenesis can also promote motility and invasion in the MDA-MB-231 breast cancer cell line. Our results indicate that, extracellularly, APC engages EPCR, PAR-1, and EGFR in order to increase the invasiveness of MDA-MB-231 cells. APC activation of matrix metalloprotease (MMP) -2 and/or -9 is necessary but not sufficient to increase invasion, and APC does not utilize the endogenous plasminogen activation system to increase invasion. Intracellularly, APC activates ERK, Akt, and NF kappa B, but not the JNK pathway to promote MDA-MB-231 cell motility. Similar to the hemostatic protease thrombin, APC has the ability to enhance both endothelial cell motility/angiogenesis and breast cancer cell migration. (C) 2009 Elsevier Inc. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available