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The Role of the Protein C and Urokinase Systems in Prostate Cancer
Author(s) -
Williams Ryan,
Glasscock Laura,
Pardhanani Pooja,
Brunson Lacey
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.lb458
Subject(s) - vitronectin , urokinase receptor , plasminogen activator , cancer research , urokinase , prostate cancer , matrigel , cell migration , cancer , secretion , cancer cell , plasminogen activator inhibitor 1 , biology , cell , chemistry , angiogenesis , medicine , endocrinology , biochemistry , integrin
The objective of this study was to determine how the protein C and urokinase systems regulate prostate tumor cell migration. Prostate cancer (CaP) is the most frequently diagnosed cancer among males, with an estimated 238,590 new cases arising in the United States during 2013. Urokinase plasminogen activator (uPA) and its inhibitor, plasminogen activator inhibitor‐1 (PAI‐1), are regulators of blood coagulation and normal cell migration. Abnormal secretion of these two proteins by neoplastic cells in the tumor microenvironment has been linked to an increased likelihood of (CaP) invasion. Using a modified Boyden chamber, we tested the ability of activated protein C (APC), uPA, PAI‐1 and vitronectin (VN), an ECM protein, to mediate uPA and PAI‐1 dependent migration of the DU‐145 CaP cell line through Matrigel. As has been shown for ovarian cancer, in the presence of uPA and PAI‐1, APC competed with uPA for binding to PAI‐1, enabling uPA to increase the invasiveness of DU‐145 cells. We also determined that VN acts as a cofactor that accelerates APC‐PAI‐1 interaction, potentially allowing once inhibited uPA to degrade ECM and give neoplastic cells room to invade through tissue. We conclude that although protein C and APC alone do not affect CaP cell invasion, in the presence of uPA and PAI‐1, APC binds to PAI‐1, freeing uPA to facilitate CaP tumor cell invasion.