title: Thrombin-unique coagulation system protein with multifaceted impacts on cancer and metastasis.
abstract: The association between blood coagulation and cancer development is well recognized. Thrombin, the pleiotropic enzyme best known for its contribution to fibrin formation and platelet aggregation during vascular hemostasis, may also trigger cellular events through protease-activated receptors, PAR-1 and PAR-4, leading to cancer progression. Our pioneering findings provided evidence that thrombin contributes to cancer metastasis by increasing adhesive potential of malignant cells. However, there is evidence that thrombin regulates every step of cancer dissemination: (1) cancer cell invasion, detachment from primary tumor, migration; (2) entering the blood vessel; (3) surviving in vasculature; (4) extravasation; (5) implantation in host organs. Recent studies have provided new molecular data about thrombin generation in cancer patients and the mechanisms by which thrombin contributes to transendothelial migration, platelet/tumor cell interactions, angiogenesis, and other processes. Though a great deal is known regarding the role of thrombin in cancer dissemination, there are new data for multiple thrombin-mediated events that justify devoting focus to this topic with a comprehensive approach.
authors.affiliation: Department of Oncology, Medical University of Bialystok, 12 Ogrodowa St., 15-025, Bialystok, Poland. mzwojtukiewicz@gmail.com.|Department of Clinical Oncology, Comprehensive Cancer Center in Bialystok, Bialystok, Poland. mzwojtukiewicz@gmail.com.
authors.forename: Marek Z
authors.initials: MZ
authors.lastname: Wojtukiewicz
authors.affiliation: Department of Oncology, Medical University of Bialystok, 12 Ogrodowa St., 15-025, Bialystok, Poland.|Department of Radiotherapy, Comprehensive Cancer Center in Bialystok, Bialystok, Poland.
authors.forename: Dominika
authors.initials: D
authors.lastname: Hempel
authors.affiliation: Department of Oncology, Medical University of Bialystok, 12 Ogrodowa St., 15-025, Bialystok, Poland.|Department of Radiotherapy, Comprehensive Cancer Center in Bialystok, Bialystok, Poland.
authors.forename: Ewa
authors.initials: E
authors.lastname: Sierko
authors.affiliation: Bioactive Lipids Research Program, Department of Pathology-School of Medicine, Wayne State University, Detroit, MI, USA.
authors.forename: Stephanie C
authors.initials: SC
authors.lastname: Tucker
authors.affiliation: Bioactive Lipids Research Program, Department of Pathology-School of Medicine, Wayne State University, Detroit, MI, USA.|Department of Chemistry, Wayne State University, Detroit, MI, USA.|Department of Oncology, Karmanos Cancer Institute, Detroit, MI, USA.
authors.forename: Kenneth V
authors.initials: KV
authors.lastname: Honn
mesh_terms: D000818:Animals; D015415:Biomarkers; D001777:Blood Coagulation; D001792:Blood Platelets / Q000378:metabolism; D002449:Cell Aggregation; D002450:Cell Communication; D002470:Cell Survival; D058750:Epithelial-Mesenchymal Transition; D006801:Humans; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology; D009360:Neoplastic Cells, Circulating / Q000378:metabolism; D009389:Neovascularization, Pathologic / Q000378:metabolism; D010641:Phenotype; D011485:Protein Binding; D015398:Signal Transduction; D013917:Thrombin / Q000378:metabolism*; D059016:Tumor Microenvironment
chemical_list: D015415:Biomarkers; D013917:Thrombin
keywords: CTCs; Cancer invasion; Metastasis; Microenvironment; PAR-1; Thrombin; Transendothelial migration