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PMID:12759260

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Citation

Woodman, SE, Ashton, AW, Schubert, W, Lee, H, Williams, TM, Medina, FA, Wyckoff, JB, Combs, TP and Lisanti, MP (2003) Caveolin-1 knockout mice show an impaired angiogenic response to exogenous stimuli. Am. J. Pathol. 162:2059-68

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.

Links

PubMed PMC1868145 Online version:10.1016/S0002-9440(10)64337-4

Keywords

Animals; Capillaries/pathology; Capillaries/ultrastructure; Caveolae/pathology; Caveolae/ultrastructure; Caveolin 1; Caveolin 2; Caveolins/genetics; Caveolins/metabolism; Collagen; Drug Combinations; Endothelium, Vascular/pathology; Endothelium, Vascular/ultrastructure; Fibroblast Growth Factor 2/pharmacology; Genotype; Laminin; Mice; Mice, Inbred C57BL; Mice, Knockout; Microscopy, Confocal/methods; Microscopy, Electron; Neoplasm Transplantation; Neoplasms, Experimental/blood supply; Neoplasms, Experimental/genetics; Neoplasms, Experimental/prevention & control; Neovascularization, Pathologic/pathology; Neovascularization, Pathologic/prevention & control; Neovascularization, Physiologic/drug effects; Proteoglycans; Tumor Cells, Cultured

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:FGF2

acts_upstream_of_or_within

GO:0045766: positive regulation of angiogenesis

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:102709

P

Seeded From UniProt

complete

MOUSE:CAV1

acts_upstream_of_or_within

GO:0070836: caveola assembly

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:2180372

P

  • occurs_in:(CL:0000071)
  • occurs_in:(EMAPA:32743)

Seeded From UniProt

complete

MOUSE:CAV1

acts_upstream_of_or_within

GO:0070836: caveola assembly

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:2180372

P

  • occurs_in:(EMAPA:32743)
  • occurs_in:(CL:0000071)

Seeded From UniProt

complete

MOUSE:CAV1

acts_upstream_of_or_within

GO:0001525: angiogenesis

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:95516

P

Seeded From UniProt

complete


See also

References

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