1: Am J Pathol. 2007 Oct 4; [Epub ahead of print] Caveolin-1 Is Critical for the Maturation of Tumor Blood Vessels through the Regulation of Both Endothelial Tube Formation and Mural Cell Recruitment. Dewever J, Frérart F, Bouzin C, Baudelet C, Ansiaux R, Sonveaux P, Gallez B, Dessy C, Feron O. From the Unit of Pharmacology and Therapeutics (UCL-FATH 5349),* and the Biomedical Magnetic Resonance Unit, Université catholique de Louvain, Brussels, Belgium. In the normal microvasculature, caveolin-1, the structural protein of caveolae, modulates transcytosis and paracellular permeability. Here, we used caveolin-1-deficient mice (Cav(-/-)) to track the potential active roles of caveolin-1 down-modulation in the regulation of vascular permeability and morphogenesis in tumors. In B16 melanoma-bearing Cav(-/-) mice, we found that fibrinogen accumulated in early-stage tumors to a larger extent than in wild-type animals. These results were confirmed by the observations of a net elevation of the interstitial fluid pressure and a relative deficit in albumin extravasation in Cav(-/-) tumors (versus healthy tissues). Immunostaining analyses of Cav(-/-) tumor sections further revealed a higher density of CD31-positive vascular structures and a dramatic deficit in alpha-smooth muscle actin-stained mural cells. The increase in blood plasma volume in Cav(-/-) tumors was confirmed by dynamic contrast enhanced-magnetic resonance imaging and found to be associated with a more rapid tumor growth. Finally, an in vitro wound test and the aorta ring assay revealed that silencing caveolin expression could directly impair the migration and the outgrowth of smooth muscle cells/pericytes, particularly in response to platelet-derived growth factor. In conclusion, a decrease in caveolin abundance, by promoting angiogenesis and preventing its termination by mural cell recruitment, appears as an important control point for the formation of new tumor blood vessels. Caveolin-1 therefore has the potential to be a marker of tumor vasculature maturity that may help adjusting anticancer therapies. PMID: 17916598 [PubMed - as supplied by publisher] Related Links Caveolin-1 expression is critical for vascular endothelial growth factor-induced ischemic hindlimb collateralization and nitric oxide-mediated angiogenesis. [Circ Res. 2004] PMID:15205364 Caveolin-1/3 double-knockout mice are viable, but lack both muscle and non-muscle caveolae, and develop a severe cardiomyopathic phenotype. [Am J Pathol. 2002] PMID:12057923 Microvascular hyperpermeability in caveolin-1 (-/-) knock-out mice. Treatment with a specific nitric-oxide synthase inhibitor, L-NAME, restores normal microvascular permeability in Cav-1 null mice. [J Biol Chem. 2002] PMID:12167625 Caveolin-1-deficient mice have increased tumor microvascular permeability, angiogenesis, and growth. [Cancer Res. 2007] PMID:17363608 Antitumor effects of in vivo caveolin gene delivery are associated with the inhibition of the proangiogenic and vasodilatory effects of nitric oxide. [FASEB J. 2005] PMID:15623570