title: The plasminogen activation system in tumor growth, invasion, and metastasis.
abstract: Generation of the serine proteinase plasmin from the extracellular zymogen plasminogen can be catalyzed by either of two other serine proteinases, the urokinase- and tissue-type plasminogen activators (uPA and tPA). The plasminogen activation system also includes the serpins PAI-1 and PAI-2, and the uPA receptor (uPAR). Many findings, gathered over several decades, strongly suggest an important and causal role for uPA-catalyzed plasmin generation in cancer cell invasion through the extracellular matrix. Recent evidence suggests that the uPA system is also involved in cancer cell-directed tissue remodeling. Moreover, the system also supports cell migration and invasion by plasmin-independent mechanisms, including multiple interactions between uPA, uPAR, PAI-1, extracellular matrix proteins, integrins, endocytosis receptors, and growth factors. These interactions seem to allow temporal and spatial reorganizations of the system during cell migration and a selective degradation of extracellular matrix proteins during invasion. The increased knowledge about the plasminogen activation system may allow utilization of its components as targets for anti-invasive therapy.
authors.affiliation: Department of Molecular and Structural Biology, Aarhus University, Denmark. pa@mbio.aau.dk
authors.forename: P A
authors.initials: PA
authors.lastname: Andreasen
authors.forename: R
authors.initials: R
authors.lastname: Egelund
authors.forename: H H
authors.initials: HH
authors.lastname: Petersen
mesh_terms: D000818:Animals; D018929:Cell Culture Techniques; D002455:Cell Division; D002465:Cell Movement; D005341:Fibrinolysin / Q000378:metabolism; D006801:Humans; D009361:Neoplasm Invasiveness / Q000473:pathology*; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology* / Q000628:therapy; D010958:Plasminogen / Q000378:metabolism*; D010960:Plasminogen Activators / Q000378:metabolism; D015849:Plasminogen Inactivators / Q000378:metabolism; D015398:Signal Transduction; D019096:Vitronectin / Q000378:metabolism
chemical_list: D015849:Plasminogen Inactivators; D019096:Vitronectin; D010958:Plasminogen; D010960:Plasminogen Activators; D005341:Fibrinolysin