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Published on: July 17, 2020
Protein C and its inhibitor in malignancy
1Department of Molecular Pathobiology, Mie University Graduate School of Medicine, Tsu-city, Mie, Japan. suzuki@doc.medic.mie-u.ac.jp
Seminars in Thrombosis and Hemostasis
|November 15, 2007
Summary
Activated protein C (APC) promotes cancer invasion and angiogenesis, while protein C inhibitor (PCI) suppresses tumor growth, metastasis, and angiogenesis. Both proteins play significant roles in malignancy.
Area of Science:
- Biochemistry
- Oncology
- Molecular Biology
Background:
- Activated protein C (APC) and protein C inhibitor (PCI) are key regulators of the protein C pathway.
- Emerging evidence highlights their roles beyond hemostasis, including in inflammation, cell proliferation, apoptosis, and cancer progression.
Purpose of the Study:
- To summarize the multifaceted roles of APC and PCI in the context of malignancy.
- To elucidate the mechanisms by which APC promotes tumor invasion and angiogenesis.
- To detail the anti-cancer and anti-angiogenic effects of PCI.
Main Methods:
- Review of existing literature on APC and PCI in cancer.
- Analysis of Transwell invasion assays to assess cell migration.
- Examination of signaling pathways (MAPK, PI3K, eNOS) involved in APC-mediated effects.
- In vitro and in vivo studies evaluating PCI's impact on tumor growth, metastasis, and angiogenesis.
Main Results:
- APC enhances ovarian cancer and choriocarcinoma cell invasion, potentially via urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor (PAI)-1.
- APC may increase breast cancer cell invasion and chemotaxis through endothelial protein C receptor (EPCR) and protease-activated receptor (PAR)-1.
- APC promotes vascular endothelial cell proliferation and angiogenesis.
- PCI expression is decreased in renal carcinoma cells.
- PCI inhibits in vitro invasion of renal carcinoma and breast cancer cells.
- PCI suppresses breast cancer growth and metastasis in vivo, independent of its protease inhibitory activity.
- PCI inhibits angiogenesis both in vitro and in vivo.
Conclusions:
- APC promotes tumor cell invasion and angiogenesis through EPCR- and PAR-1-mediated pathways.
- PCI exhibits dual mechanisms in inhibiting tumor progression: protease-dependent inhibition of invasion and protease-independent suppression of growth, metastasis, and angiogenesis.
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