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      Polyoma Middle T-induced Vascular Tumor Formation: The Role of the Plasminogen Activator/Plasmin System

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          Abstract

          The middle T antigen of murine Polyomavirus (PymT) rapidly transforms endothelial cells, leading to the formation of vascular tumors in newborn mice. Transformed endothelial (End.) cell lines established from such tumors exhibit altered proteolytic activity as a result of increased expression of urokinase-type plasminogen activator (uPA) and are capable of inducing vascular tumors efficiently when injected into adult mice. In this study we have used mice lacking components of the PA/plasmin system to analyze the role of this system in the transformation process and in tumor growth. We found that the proteolytic status of the host is not a critical determinant for PymT-induced vascular tumor formation. In addition, the lack of either uPA or tissue-type PA (tPA) activity is not limiting for the establishment and proliferation of End. cells in vitro, although the combined loss of both PA activities leads to a marked reduction in proliferation rates. Furthermore, the in vitro morphogenetic properties of mutant End. cells in fibrin gels could only be correlated with an altered proteolytic status in cells lacking both uPA and tPA. However, in contrast with tumors induced by PymT itself, the tumorigenic potential of mutant and wild-type End. cell lines was found to be highly dependent on the proteolytic status of both the tumor cells and the host. Thus, genetic alterations in the PA/plasmin system affect vascular tumor development, indicating that this system is a causal component in PymTmediated oncogenesis.

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          Most cited references 21

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          Physiological consequences of loss of plasminogen activator gene function in mice.

          Indirect evidence suggests a crucial role for the fibrinolytic system and its physiological triggers, tissue-type (t-PA) and urokinase-type (u-PA) plasminogen activator, in many proteolytic processes. Inactivation of the t-PA gene impairs clot lysis and inactivation of the u-PA gene results in occasional fibrin deposition. Mice with combined t-PA and u-PA deficiency suffer extensive spontaneous fibrin deposition, with its associated effects on growth, fertility and survival.
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            Plasminogen activators, tissue degradation, and cancer.

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              The plasminogen activator/plasmin system.

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                Author and article information

                Journal
                J Cell Biol
                The Journal of Cell Biology
                The Rockefeller University Press
                0021-9525
                1540-8140
                19 May 1997
                : 137
                : 4
                : 953-963
                Affiliations
                [* ]Research Institute of Molecular Pathology, University of Vienna, A-1030 Vienna, Austria; []Ontario Cancer Institute, Toronto, Ontario, Canada; [§ ]Department of Morphology, []Department of Pathology, University Medical Center, CH-1211 Geneva 4, Switzerland; []Max-Planck Institute for Physiological and Clinical Research, Department of Molecular and Cell Biology, D-61231 Bad Nauheim, Germany; and [** ]Center for Transgene Technology and Gene Therapy, Flanders Interuniversity Institute for Biotechnology, B-3000 Leuven, Belgium
                Article
                2139839
                9151696
                Categories
                Article

                Cell biology

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