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Host-derived plasminogen activator inhibitor-1 (PAI-1) concentration is critical for in vivo tumoral angiogenesis and growth
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Host-derived plasminogen activator inhibitor-1 (PAI-1) concentration is critical for in vivo tumoral angiogenesis and growth
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Journal Article
Host-derived plasminogen activator inhibitor-1 (PAI-1) concentration is critical for in vivo tumoral angiogenesis and growth
2004
Overview
Plasminogen activator inhibitor type 1 (PAI-1) plays a key role in tumor progression and is believed to control proteolytic activity and cell migration during angiogenesis. We report here that host PAI-1, at physiological concentration, promotes
in vivo
tumor invasion and angiogenesis. In sharp contrast, inhibition of tumor vascularization was observed when PAI-1 was produced at supraphysiologic levels, either by host cells (transgenic mice overexpressing PAI-1) or by tumor cells (after transfection with murine PAI-1 cDNA). This study provides for the first time
in vivo
evidence for a dose-dependent effect of PAI-1 on tumor angiogenesis. Of great interest is the finding that PAI-1 produced by tumor cells, even at high concentration, did not overcome the absence of PAI-1 in the host, emphasizing the importance of the cellular source of PAI-1.
Publisher
Nature Publishing Group UK,Nature Publishing,Nature Publishing Group
Subject
/ Animals
/ Biochemistry, biophysics & molecular biology
/ Biochimie, biophysique & biologie moléculaire
/ Biological and medical sciences
/ Biology
/ Cell differentiation, maturation, development, hematopoiesis
/ Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes
/ Collagen
/ Fundamental and applied biological sciences. Psychology
/ Medicine
/ Mice
/ Molecular and cellular biology
/ Neoplasms, Experimental - blood supply
/ Neoplasms, Experimental - pathology
/ Neovascularization, Pathologic - etiology
/ Oncology
/ PAI-1
/ Plasminogen Activator Inhibitor 1 - analysis
/ Plasminogen Activator Inhibitor 1 - physiology
/ Plasminogen activator inhibitors
/ Sciences de la santé humaine
/ Tumors
