title: The relationship between tissue factor and cancer progression: insights from bench and bedside.
abstract: It is now widely recognized that a strong correlation exists between cancer and aberrant hemostasis. Patients with various types of cancers, including pancreatic, colorectal, and gastric cancer, often develop thrombosis, a phenomenon commonly referred to as Trousseau syndrome. Reciprocally, components from the coagulation cascade also influence cancer progression. The primary initiator of coagulation, the transmembrane receptor tissue factor (TF), has gained considerable attention as a determinant of tumor progression. On complex formation with its ligand, coagulation factor VIIa, TF influences protease-activated receptor-dependent tumor cell behavior, and regulates integrin function, which facilitate tumor angiogenesis both in vitro and in mouse models. Furthermore, evidence exists that an alternatively spliced isoform of TF also affects tumor growth and tumor angiogenesis. In patient material, TF expression and TF cytoplasmic domain phosphorylation correlate with disease outcome in many, but not in all, cancer subtypes, suggesting that TF-dependent signal transduction events are a potential target for therapeutic intervention in selected types of cancer. In this review, we summarize our current understanding of the role of TF in tumor growth and metastasis, and speculate on anticancer therapy by targeting TF.
authors: Department of Thrombosis and Hemostasis, Einthoven Laboratory for Experimental Vascular Medicine, Leiden Univerisity Medical Center, Leiden, The Netherlands.
authors: Yascha W
authors: YW
authors: van den Berg
authors: Susanne
authors: S
authors: Osanto
authors: Pieter H
authors: PH
authors: Reitsma
authors: Henri H
authors: HH
authors: Versteeg
mesh_terms: D017398:Alternative Splicing; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use; D016503:Drug Delivery Systems; D015942:Factor VIIa / Q000378:metabolism; D006801:Humans; D016023:Integrins / Q000378:metabolism; D058990:Molecular Targeted Therapy; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology*; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology*; D020033:Protein Isoforms / Q000037:antagonists & inhibitors / Q000378:metabolism; D044464:Receptor, PAR-2 / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013925:Thromboplastin / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013927:Thrombosis / Q000209:etiology* / Q000517:prevention & control
chemical_list: D000970:Antineoplastic Agents; D016023:Integrins; D009363:Neoplasm Proteins; D020033:Protein Isoforms; D044464:Receptor, PAR-2; D013925:Thromboplastin; D015942:Factor VIIa