By lessening the level of a protein, DeBusk et al. bring pathological angiogenesis to a halt.
Formerly known for its effects on neuronal growth, the protein δ-catenin is now found to be highly expressed in human vascular endothelial cells where it assists vessel growth. Although this is the first report of δ-catenin in vessels, other proteins are known to function in both vascular and neuronal networks, which grow side-by-side in the developing embryo. In vessels, δ-catenin acted as it does in neurons, assisting cell motility by activating Rho GTPases.
Vessels grew normally in the healthy tissues of mice that lacked one or both of the δ-catenin–encoding alleles. The resulting paucity of δ-catenin disrupted only vessel growth associated with tumors and healing wounds. Inflammation, which often coincides with cancer, triggered δ-catenin through the transcriptional regulator NF-kB. In samples from patients with lung cancer, the team found that tumors expressed more δ-catenin than did the surrounding tissue.
Children bearing defects in one δ-catenin allele acquire a lethal disorder, Cri-du-chat syndrome, which is characterized by neuronal, developmental, and heart defects. Before now, these effects were considered strictly neuronal in nature. But because vascular endothelial cell motility is essential for heart development, the authors speculate that low levels of δ-catenin may also underlie the patients' cardiovascular abnormalities.
δ-catenin may be a promising anti-cancer target because eliminating or reducing its expression stunts only inflammation-induced vessel growth. First, however, the side effects on neuronal development must be investigated.
