Abstract 3479: Claudin-14: A novel regulator of angiogenesis

Angiogenesis, the formation of new blood vessels from pre-existing ones, is vital for tumor growth and spread. A better understanding of angiogenic processes, particularly cell-cell adhesion, is required for the development of effective anti-angiogenic drugs. Claudin-14 (Cldn14) is a component of Tight Junctions (TJ) and its function in angiogenesis is not yet known. Other TJ molecules such as JAMs are known to be involved in angiogenesis; for example, we have identified a novel dosage-dependent role for JAM-B in the regulation of angiogenesis in the context of trisomy of human chromosome 21 (Hsa21) genes (Reynolds et al. Nature 2010); Cldn14 is also present on Hsa21. Therefore we hypothesise that Cldn14 may also play a role in the regulation of angiogenesis. Here we show that depletion of Cldn14 enhances VEGF-stimulated angiogenesis in the ex vivo aortic ring assay and increases primary mouse lung endothelial cell proliferation via changes in downstream signalling. Viable Cldn14 knockout mice exhibit normal vasculature in unchallenged organs, suggesting that the effect may be specific to pathological states. These data reveal novel regulatory roles for Cldn14 and future work will characterise further the functions of Cldn14 in angiogenesis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3479. doi:10.1158/1538-7445.AM2011-3479