Linked Life Data

18000793

Source:http://linkedlifedata.com/resource/pubmed/id/18000793

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7
pubmed:dateCreated
2007-11-16
pubmed:abstractText
Activated protein C (APC) and protein C inhibitor (PCI) are the major components of the anticoagulant protein C pathway. Recently, APC and PCI have been demonstrated to play many roles not only in the regulation of hemostasis but also in cell inflammation, proliferation, apoptosis, tumor cell migration, invasion, and metastasis. Here we summarize the role of APC and PCI in malignancy. APC increases migration of ovarian cancer cells and choriocarcinoma cells in a Transwell invasion assay in the presence of plasminogen activator inhibitor (PAI)-1; this finding suggests that APC stimulates urokinase-type plasminogen activator (uPA) by forming a complex with PAI-1 leading to activation of extracellular matrix proteases and increased invasion. It was recently reported that APC, independent of PAI-1, may increase invasion and chemotaxis of breast cancer cells by activating specific signaling pathways through endothelial protein C receptor (EPCR) and protease-activated receptor (PAR)-1. APC also increased proliferation of vascular endothelial cells and angiogenesis by EPCR-mediated activation of mitogen-activated protein kinase (MAPK), phosphatidylinositol 3-kinase (PI3K), and endothelial nitric oxide synthase (eNOS) pathways. On the other hand, we have previously reported that both uPA and PCI are synthesized in renal proximal tubular epithelial cells (RPTECs) and that PCI expression in RPTEC-derived tumor cells is significantly decreased compared with normal RPTECs. The RPTEC-derived renal carcinoma cell line Caki-1 also showed decreased expression of PCI. PCI inhibited in vitro invasive activity of Caki-1 and breast cancer cells by its protease inhibitory activity. However, PCI was found to inhibit the growth and metastatic potential of breast cancer cells independent of its protease inhibitory activity in severe combined immunodeficient mice. PCI can also inhibit angiogenesis in vivo and in vitro assays independent of its protease inhibitory activity. Overall, these data show that APC promotes tumor cell invasion by EPCR-mediated and PAR-1-mediated protease activity and that PCI inhibits tumor cell invasion in vitro by its protease inhibitory activity and suppresses tumor cell growth, metastasis, and angiogenesis independent of its protease inhibitory activity.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Angiogenesis Inducing Agents, http://linkedlifedata.com/resource/pubmed/chemical/Angiogenesis Inhibitors, http://linkedlifedata.com/resource/pubmed/chemical/Anticoagulants, http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD, http://linkedlifedata.com/resource/pubmed/chemical/Fibrinolytic Agents, http://linkedlifedata.com/resource/pubmed/chemical/PROCR protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Plasminogen Activator Inhibitor 1, http://linkedlifedata.com/resource/pubmed/chemical/Protein C, http://linkedlifedata.com/resource/pubmed/chemical/Protein C Inhibitor, http://linkedlifedata.com/resource/pubmed/chemical/Receptor, PAR-1, http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Cell Surface, http://linkedlifedata.com/resource/pubmed/chemical/Serine Proteinase Inhibitors
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0094-6176
pubmed:author
pubmed:issnType
Print
pubmed:volume
33
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
667-72
pubmed:meshHeading
pubmed:year
2007
pubmed:articleTitle
Protein C and its inhibitor in malignancy.
pubmed:affiliation
Department of Molecular Pathobiology, Mie University Graduate School of Medicine, Tsu-city, Mie, Japan. suzuki@doc.medic.mie-u.ac.jp
pubmed:publicationType
Journal Article, Review, Research Support, Non-U.S. Gov't