TY - JOUR
T1 - Caveolin-1 knockout mice show an impaired angiogenic response to exogenous stimuli
AU - Woodman, Scott E.
AU - Ashton, Anthony W.
AU - Schubert, William
AU - Lee, Hyangkyu
AU - Williams, Terence M.
AU - Medina, Freddy A.
AU - Wyckoff, Jeffrey B.
AU - Combs, Terry P.
AU - Lisanti, Michael P.
N1 - 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.).
PY - 2003/6/1
Y1 - 2003/6/1
N2 - 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.
AB - 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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U2 - 10.1016/S0002-9440(10)64337-4
DO - 10.1016/S0002-9440(10)64337-4
M3 - Article
C2 - 12759260
AN - SCOPUS:0038075402
SN - 0002-9440
VL - 162
SP - 2059
EP - 2068
JO - American Journal of Pathology
JF - American Journal of Pathology
IS - 6
ER -