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.
Written by:
Roudnicky F, Poyet C, Wild P, Krampitz S, Negrini F, Huggenberger R, Rogler A, Stöhr R, Hartmann A, Provenzano M, Otto VI, Detmar M. Are you the author?
Institute of Pharmaceutical Sciences, ETH Zurich; Departments of Urology and Pathology, University Hospital Zurich, Zurich, Switzerland; and Department of Urology, University Hospital Erlangen, Erlangen, Germany
Reference: Cancer Res. 2013 Feb 1;73(3):1097-106
doi: 10.1158/0008-5472.CAN-12-1855
PubMed Abstract
PMID: 23243026
