Heterozygous deficiency of δ-catenin impairs pathological angiogenesis

δ-catenin expression in vascular endothelial cells is boosted by inflammatory cytokines, , and that δ-catenin deficiency impairs tumor angiogenesis in mice,and that δ-catenin deficiency impairs tumor angiogenesis in mice.

About the Cover:

DeBusk et al. find that δ-catenin expression in vascular endothelial cells is boosted by inflammatory cytokines, and that δ-catenin deficiency impairs tumor angiogenesis in mice. The original immunofluorescence image (right) shows the endothelial marker CD31 (green) in tumor tissue sections from mice injected subcutaneously with Lewis lung carcinoma cells. Artwork by Joshua Graver (joshuagraver@mac.com).

Abstract:

Vascular and neuronal networks share a similar branching morphology, and emerging evidence implicates common mechanisms in the formation of both systems. delta-Catenin is considered a neuronal catenin regulating neuron cell-cell adhesion and cell motility. Here, we report expression of delta-catenin in vascular endothelium, and show that deletion of only one allele of delta-catenin is sufficient to impair endothelial cell motility and vascular assembly in vitro and pathological angiogenesis in vivo, thereby inhibiting tumor growth and wound healing. In contrast, deletion of one or both allele of delta-catenin had no effects on hormone-induced physiological angiogenesis in the uterus. Molecular analysis confirmed a gene dosage effect of delta-catenin on Rho GTPase activity. Moreover, we show that inflammatory cytokines, but not angiogenic factors, regulate delta-catenin expression, and the levels of delta-catenin positively correlate to human lung cancers. Collectively, our data suggest that inflammation, commonly associated with disease conditions, induces delta-catenin expression that specifically regulates pathological, and not physiological, angiogenesis. Because only pathological angiogenesis is sensitive to decreased levels of delta-catenin, this may provide a good target for antiangiogenic therapy.

Lab/Branch/Program: 
Cancer and Inflammation Program
Citation: 

Heterozygous deficiency of δ-catenin impairs pathological angiogenesis.  DeBusk LM, Boelte K, Min Y, Lin PC. J Exp Med 207(1): 77-84, 2010.

Published Date: 
January, 2010