The plasminogen activation system in tumor growth, invasion, and metastasis |
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Authors: | P. A. Andreasen R. Egelund H. H. Petersen |
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Affiliation: | (1) Cellular Protein Science Laboratory, Department of Molecular and Structural Biology, Aarhus University, 10C Gustav Wied’s Vej, 8000 Aarhus C (Denmark), Fax +45 8612 3178, e-mail: pa@mbio.aau.dk, DK |
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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. |
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Keywords: | . Serine proteinases serpins integrins cell migration anti-invasive therapy. |
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