Caveolin-1 Knockout Mice Show an Impaired Angiogenic Response to Exogenous Stimuli
| Autor: | William Schubert, Anthony W. Ashton, Terence M. Williams, Terry P. Combs, Freddy A. Medina, Hyangkyu Lee, Jeffrey B. Wyckoff, Michael P. Lisanti, Scott Eric Woodman |
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| Rok vydání: | 2003 |
| Předmět: |
Pathology
medicine.medical_specialty Genotype Angiogenesis Caveolin 2 Caveolin 1 Basic fibroblast growth factor Neovascularization Physiologic Biology Caveolae Caveolins Pathology and Forensic Medicine Mice chemistry.chemical_compound Tumor Cells Cultured medicine Animals Mice Knockout Matrigel Microscopy Confocal Neovascularization Pathologic Neoplasms Experimental Capillaries Cell biology Mice Inbred C57BL Drug Combinations Microscopy Electron medicine.anatomical_structure chemistry Knockout mouse cardiovascular system Fibroblast Growth Factor 2 Proteoglycans Animal Model Collagen Endothelium Vascular Laminin Neoplasm Transplantation Blood vessel |
| Zdroj: | The American Journal of Pathology. 162:2059-2068 |
| ISSN: | 0002-9440 |
| Popis: | Recent studies have shown that caveolin-1 (Cav-1) plays an important role as a regulator of angiogenesis in vitro. Here, we use Cav-1 knockout (KO) mice as a model system to examine the in vivo relevance of these findings. A primary mediator of angiogenesis is basic fibroblast growth factor (bFGF). Thus, we studied bFGF-induced angiogenesis in Cav-1 KO mice using a reconstituted basement membrane system, ie, Matrigel plugs, supplemented with bFGF. In Cav-1 KO mice, implanted Matrigel plugs showed a dramatic reduction in both vessel infiltration and density, as compared with identical plugs implanted in wild-type control mice. We also examined the necessity of Cav-1 to support the angiogenic response of an exogenous tumor by subcutaneously injecting Cav-1 KO mice with the melanoma cell line, B16-F10. We show that tumor weight, volume, and vessel density are all reduced in Cav-1 KO mice, consistent with diminished angiogenesis. Ultrastructural analysis of newly formed capillaries within the exogenous tumors reveals a lack of endothelial caveolae and incomplete capillary formation in Cav-1 KO mice. These results provide novel evidence that Cav-1 and caveolae play an important positive role in the process of pathological angiogenesis in vivo. |
| Databáze: | OpenAIRE |
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