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]

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