Experimental evidence using animal models has proven the efficacy of targeting a tumor endothelial marker (TEM) in eradicating large solid tumours. It follows that a well characterised tumor endothelial marker would offer much promise as an anti-cancer target. Despite many efforts by numerous groups, a well defined tumor endothelial marker in man has remained elusive. CLEC14A is a novel endothelial specific C-type lectin that is a member of the endosialin/TEM1 and thrombomodulin family of lectins. Protein sequence alignment of CLEC14A shows conservation from fish to man and endothelial specificity of expression is seen in the embryonic zebrafish. Detailed analysis of CLEC14A expression using human tissue arrays showed that CLEC14A is absent in human adult tissue but highly expressed in endothelium across a wide range of tumour tissues. CLEC14A is a superior tumor endothelial marker to Robo4 in terms of specificity and level of expression on the cell surface. CLEC14A is only expressed by endothelium in the absence of shear stress and this could explain its tumor specific expression due to poor blood flow in ill-formed tumor vessels. Functional studies have shown that CLEC14A is present on filopodia and mediates endothelial cell migration and tube formation. Anti-sera to CLEC14A similarly inhibited these processes suggesting that anti-CLEC14A monoclonal antibodies would have anti-angiogenic activity. The expression profile of CLEC14A, its cell surface localisation and inhibition of pro-angiogenic activities by anti-sera make CLEC14A a uniquely interesting target.

Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1589.