Vascular endocan is preferentially expressed in tumor endothelium

Abstract

Endothelial cell phenotypes are differentially regulated between different sites of the vascular tree. We tested the hypothesis that endocan, a novel soluble dermatan sulfate proteoglycan, is differentially expressed in the intact endothelium and that site-specific expression is mediated by signals in the local microenvironment. Using a combination of Northern blot analyses, Taqman RT-PCR, and in situ hybridizations, endocan was shown to be preferentially expressed in the endothelial lining of tumor xenografts, including human non-small cell lung cancer, rat glioma, and human renal cell carcinoma. In contrast, endocan mRNA was expressed at low levels in embryos between E4.5 and E18.5. Under in vitro conditions, endocan expression in human umbilical vein endothelial cells (HUVEC) was upregulated by tumor cell-conditioned medium, an effect that was inhibited by the addition of neutralizing antibody to vascular endothelial growth factor (VEGF). Moreover, treatment of HUVEC with VEGF resulted in a dose- and time-dependent increase in endocan mRNA. The results suggest that endocan is preferentially expressed in tumor endothelium in vivo and that its expression is regulated by tumor-derived factors.