The Plasminogen Activator System and Cancer

Abstract

The fibrinolytic system, more appropriately referred to as the plasminogen activator system, controls not only the intravascular fibrin deposition but also participates in a wide variety of physiologic and pathologic processes. In cancer, the components of this system are involved in tumor growth, invasion and metastasis, through their effect on angiogenesis and cell migration. These components are found in most tumors and their expression signifies not only their function but also carries a prognostic value. Their expression is in turn modulated by cytokines and growth factors, many of which are up-regulated in cancer. Though both plasminogen activators, tPA and uPA, are expressed in tumor cells, uPA with its receptor (uPAR) is mostly involved in cellular functions, while tPA with its receptor annexin II on endothelial surface regulates intravascular fibrin deposition. Among the inhibitors of fibrinolysis, PAI-1 is a major player in the pathogenesis of many vascular diseases as well as in cancer. Therapeutic intervention, either using plasminogen activators or use of experimental inhibitor agents against PAI-1, has shown encouraging results in experimental tumors but not verified clinically. Information provided in this brief review is aimed to promote greater interest in the role of the plasminogen activator system in cancer.

Cellular and Molecular Characterization of Human Cardiac Stem Cells Reveals Key Features Essential for Their Function and Safety

“…It has been shown that matrix metalloproteinase1 (MMP1), which is involved in the breakdown of extracellular matrix proteins, plays a role in tissue remodeling and metastasis [58][59][60] through collagen destruction, which causes progression in cardiac dysfunction [61]. The role of plasminogen activator urokinase (PLAU) and plasminogen activator tissue (PLAT) in extracellular matrix degradation and possible tumor cell migration and proliferation has also been highlighted [62][63][64][65]. ell cycle-related genes were downregulated through subsequent passages.…”

Prognosis in adenocarcinomas of lower oesophagus, gastro‐oesophageal junction and cardia evaluated by uPAR‐immunohistochemistry

“…11 Plasmin degrades components of the ECM both directly and indirectly through activation of MMPs and cytokines involved in both tissue repair and malignant growth. 12,13 Several studies have shown that increased levels of uPAR is linked to poor prognosis in a number of cancers, including pulmonary carcinomas, colorectal and breast cancer. 8,[14][15][16] We recently reported that uPAR in gastric cancers is frequently expressed in cancer cell populations, 17 which are likely directly linked to the malignancy of the disseminated cancer cells in the bone marrow.…”

Levels of Angiogenesis Factors Expression in Sarcoma Tissue and Non-Malignant Lesions in Pediatric Patients: Results of a Cross-Sectional Study

“…По известным нам данным, биологическая роль различных изоформ VEGFA остается не до конца определенной [8,9,17]. Так, VEGAF121 и VEGFA165 секретируются в эндотелиальных клетках и спо-собствуют их активному митогенезу [10,11,18]. Изоформы с большим количеством аминоки-слот -VEGFA165 и VEGFA189 -ассоциируются в основном с присутствием в клетках, хотя тоже обладают сосудистой проницаемостью [10,17].…”

“…Изоформы с большим количеством аминоки-слот -VEGFA165 и VEGFA189 -ассоциируются в основном с присутствием в клетках, хотя тоже обладают сосудистой проницаемостью [10,17]. Считается, что VEGFA165 более «выгодна» для опу-холи, чем VEGFA189, хотя обе изоформы участвуют в локальном ангиогенезе [11,17,18]. Отмечено, что при дефиците VEGFA165 компенсаторно повы-шается уровень VEGFA189, однако это не сопро-вождается усилением инвазии опухоли в костный мозг [17,18].…”

“…Активаторы плазминогена урокиназного типа (Urokinase-type plasminogen activator, uPA) и его антагонист PAI1 (Plasminogen activators inhibitor-1) продуцируются нормальными и опухолевыми клетками и играют ключевую роль в деградации и ремоделировании межклеточного матрикса, деструкции базальной мембраны и метастазировании. Повышение уров-ня uPA ассоциируется с плохим прогнозом заболе-вания [11][12][13].…”