Endocan is upregulated on tumor vessels in invasive bladder cancer where it mediates VEGF-A–induced angiogenesis

F Roudnicky, C Poyet, P Wild, S Krampitz, F Negrini… - Cancer research, 2013 - AACR
F Roudnicky, C Poyet, P Wild, S Krampitz, F Negrini, R Huggenberger, A Rogler, R Stöhr…
Cancer research, 2013AACR
Tumor-associated blood vessels differ from normal vessels and proteins present only on
tumor vessels may serve as biomarkers or targets for antiangiogenic therapy in cancer.
Comparing the transcriptional profiles of blood vascular endothelium from human invasive
bladder cancer with normal bladder tissue, we found that the endothelial cell-specific
molecule endocan (ESM1) was highly elevated on tumor vessels. Endocan was associated
with filopodia of angiogenic endothelial tip cells in invasive bladder cancer. Notably …
Abstract
Tumor-associated blood vessels differ from normal vessels and proteins present only on tumor vessels may serve as biomarkers or targets for antiangiogenic therapy in cancer. Comparing the transcriptional profiles of blood vascular endothelium from human invasive bladder cancer with normal bladder tissue, we found that the endothelial cell-specific molecule endocan (ESM1) was highly elevated on tumor vessels. Endocan was associated with filopodia of angiogenic endothelial tip cells in invasive bladder cancer. Notably, endocan expression on tumor vessels correlated strongly with staging and invasiveness, predicting a shorter recurrence-free survival time in noninvasive bladder cancers. Both endocan and VEGF-A levels were higher in plasma of patients with invasive bladder cancer than healthy individuals. Mechanistic investigations in cultured blood vascular endothelial cells or transgenic mice revealed that endocan expression was stimulated by VEGF-A through the phosphorylation and activation of VEGFR-2, which was required to promote cell migration and tube formation by VEGF-A. Taken together, our findings suggest that disrupting endocan interaction with VEGFR-2 or VEGF-A could offer a novel rational strategy to inhibit tumor angiogenesis. Furthermore, they suggest that endocan might serve as a useful biomarker to monitor disease progression and the efficacy of VEGF-A–targeting therapies in patients with bladder cancer. Cancer Res; 73(3); 1097–106. ©2012 AACR.
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