Caveolin-1 knockout mice show an impaired angiogenic response to exogenous stimuli

Scott E. Woodman, Anthony W. Ashton, William Schubert, Hyangkyu Lee, Terence M. Williams, Freddy A. Medina, Jeffrey B. Wyckoff, Terry P. Combs, Michael P. Lisanti

Research output: Contribution to journalArticlepeer-review

100 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)2059-2068
Number of pages10
JournalAmerican Journal of Pathology
Volume162
Issue number6
DOIs
Publication statusPublished - 2003 Jun 1

Bibliographical note

Funding Information:
Supported by grants from the National Institutes of Health, the Muscular Dystrophy Association, the American Heart Association, and the Breast Cancer Alliance, as well as a Hirschl/Weil-Caulier Career Scientist Award (all to M. P. L.); and by a National Institutes of Health Medical Scientist Training Grant (T32-GM07288; S. E. W. and T. M. W.).

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine

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