Tumor cells secrete an angiogenic factor that stimulates basic fibroblast growth factor and urokinase expression in vascular endothelial cells
Autor: | R. Marelli, Daniel B. Rifkin, G. Della Valle, Paolo Ciana, Paolo Mignatti, S.J. Mandriota, Paul H.A. Quax, F A Peverali |
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Přispěvatelé: | TNO Preventie en Gezondheid |
Jazyk: | angličtina |
Rok vydání: | 1994 |
Předmět: |
Physiology
Angiogenesis Clinical Biochemistry Basic fibroblast growth factor Biology Vascular endothelial growth inhibitor chemistry.chemical_compound Mice Liver Neoplasms Experimental Tumor Cells Cultured Animals Humans Autocrine signalling Neovascularization Pathologic Cell Biology Urokinase-Type Plasminogen Activator Cell biology Endothelial stem cell Vascular endothelial growth factor B Vascular endothelial growth factor A Vascular endothelial growth factor C chemistry Culture Media Conditioned Angiogenesis Inducing Agents Cattle Fibroblast Growth Factor 2 Endothelium Vascular Sarcoma Experimental |
Zdroj: | Journal of cellular physiology, 161, 1-14 |
Popis: | Culture medium conditioned by human SK-Hep1 hepatoma cells or mouse S180 sarcoma cells rapidly up-regulates endothelial cell expression of basic fibroblast growth factor (bFGF) and induces formation of capillary-like structures by vascular endothelial cells grown on three-dimensional fibrin gels (in vitro angiogenesis). Incubation of endothelial cells with the tumor cell-conditioned media also results in increased expression of urokinase plasminogen activator (uPA), a key component of the proteolytic system required for cell invasion and capillary formation. Although the tumor cell-conditioned media contain no bFGF, addition of anti-recombinant bFGF IgG abolishes the up-regulation of uPA and blocks in vitro angiogenesis. This indicates that both the increase in uPA production and formation of capillary-like structures are mediated by endogenous bFGF expressed by the endothelial cells. Both the bFGF/uPA-inducing activity and the angiogenic activity of SK-Hep1 cell-conditioned medium copurify with a relatively acid-resistant peptide that has moderate affinity for heparin and M(r) < 18 kDa > 3.5 kDa. Known cytokines with similar biochemical features do not possess the same biological activity. These findings indicate that angiogenesis can be mediated by endothelial cell bFGF through an autocrine mechanism and that the bFGF-inducing peptide may represent a novel tumor-derived angiogenic factor that modulates in endothelial cells the concerted expression of cytokines and proteolytic enzymes required for capillary formation. |
Databáze: | OpenAIRE |
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