title: Caveolin-1 knockout mice show an impaired angiogenic response to exogenous stimuli.
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.
authors.affiliation: Department of Molecular Pharmacology, Einstein Cancer Center, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
authors.forename: Scott E
authors.initials: SE
authors.lastname: Woodman
authors.forename: Anthony W
authors.initials: AW
authors.lastname: Ashton
authors.forename: William
authors.initials: W
authors.lastname: Schubert
authors.forename: Hyangkyu
authors.initials: H
authors.lastname: Lee
authors.forename: Terence M
authors.initials: TM
authors.lastname: Williams
authors.forename: Freddy A
authors.initials: FA
authors.lastname: Medina
authors.forename: Jeffrey B
authors.initials: JB
authors.lastname: Wyckoff
authors.forename: Terry P
authors.initials: TP
authors.lastname: Combs
authors.forename: Michael P
authors.initials: MP
authors.lastname: Lisanti
mesh_terms: D000818:Animals; D002196:Capillaries / Q000473:pathology / Q000648:ultrastructure; D021941:Caveolae / Q000473:pathology / Q000648:ultrastructure; D051242:Caveolin 1; D051243:Caveolin 2; D022461:Caveolins / Q000235:genetics* / Q000378:metabolism; D003094:Collagen; D004338:Drug Combinations; D004730:Endothelium, Vascular / Q000473:pathology / Q000648:ultrastructure; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D005838:Genotype; D007797:Laminin; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018613:Microscopy, Confocal / Q000379:methods; D008854:Microscopy, Electron; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000098:blood supply / Q000235:genetics / Q000517:prevention & control; D009389:Neovascularization, Pathologic / Q000473:pathology / Q000517:prevention & control; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D011509:Proteoglycans; D014407:Tumor Cells, Cultured
chemical_list: C495541:Cav1 protein, mouse; D051242:Caveolin 1; D051243:Caveolin 2; D022461:Caveolins; D004338:Drug Combinations; D007797:Laminin; D011509:Proteoglycans; D016222:Fibroblast Growth Factor 2; C059485:matrigel; D003094:Collagen