Table 1 Coagulation factors and the associated regulatory proteins in EOC
From: Ovarian cancer, the coagulation pathway, and inflammation
Coagulation factors | Effects |
|---|---|
Tissue factor (TF) ↑ | Promoting angiogenesis by activation of MAPK[73] and protein C kinase C-dependent signaling[76]; TF-PAR2 selectively synergizes with PDGF-BB to enhance to metastasis in lymphnodes[78]. Promoting invasion and metastasis by the activation of P21Ras and P42/P44 MAPK pathway to inhibit apoptosis[14]; overexpressing growth factors and chemokines (i.e. IL-8)[13]. |
TF-VII-PAR2 ↑ | Promoting angiogenesis, invasion, and metastasis by clotting-independent mechanism[77] in presence of inflammatory cytokines |
Factor X ↑ | Forming complex with TF-VIIa to promote tumor angiogenesis and metastasis[14] |
Thrombin/PAR1 ↑ | Promoting angiogenesis by inhibiting EC migration to collagen type IV or to laminin[99]; upregulating VEGF expression[100]. Promoting invasion and metastasis depended on at least 6 mechanisms (text) |
Fibrinogen/fibrin ↑ | Stimulating angiogenesis; the fibrin gel matrix facilitating tumor metastasis; increasing plasma exudates to form ascites[129, 130, 132]. |
Factor XII/XI ↑ | Positive feedback on human kallikreins system |
Factor XIII ↑ | Form stable fibrin |
Regulatory proteins | |
Heparin cofactor II ↑ | Produce chemoattractant peptide for MAs migration. |
Endothelial protein C receptor ↑ | Intensifying APC-PAR1 signal transduction [205] and contributing to antiapoptosis in tumor. |
Tissue factor pathway inhibitor ↓ | Loss of control of tumor growth and metastasis by activating Factor Xa and increasing Factor Xa-PAR2 signaling[81]. |
Tissue factor pathway inhibitor-2 ↓ | Loss of Inhibiting TF-VIIa complex and various protease but not Factor Xa; Loss of antiangiogenesis and antimetastasis. |