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(American Journal of Pathology. 2003;162:2059-2068.)
© 2003 American Society for Investigative Pathology

Animal Model

Caveolin-1 Knockout Mice Show an Impaired Angiogenic Response to Exogenous Stimuli

Scott E. Woodman*{dagger}, Anthony W. Ashton{ddagger}, William Schubert*{dagger}, Hyangkyu Lee*{dagger}, Terence M. Williams*{dagger}, Freddy A. Medina*{dagger}, Jeffrey B. Wyckoff§, Terry P. Combs and Michael P. Lisanti*{dagger}

From the Departments of Molecular Pharmacology,* Cardiology,{ddagger} Anatomy and Structural Biology,§ and Cell Biology, and the Einstein Cancer Center,{dagger} Albert Einstein College of Medicine, Bronx, New York

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.




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