Evidence for Post-translational Processing of Vascular Endothelial (VE)-cadherin in Brain Tumors: Towards a Candidate Biomarker

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2013 Dec 21

PMID 24358106

Citations 8

Authors

Isabelle Vilgrain

Adama Sidibe

Helena Polena

Francine Cand

Tiphaine Mannic

Melanie Arboleas

Sandra Boccard

Antoine Baudet

Danielle Gulino-Debrac

Laurence Bouillet

Jean-Louis Quesada

Christophe Mendoza

Jean-Francois Lebas

Laurent Pelletier

Francois Berger

Affiliations

Soon will be listed here.

Abstract

Vessel abnormalities are among the most important features in malignant glioma. Vascular endothelial (VE)-cadherin is of major importance for vascular integrity. Upon cytokine challenge, VE-cadherin structural modifications have been described including tyrosine phosphorylation and cleavage. The goal of this study was to examine whether these events occurred in human glioma vessels. We demonstrated that VE-cadherin is highly expressed in human glioma tissue and tyrosine phosphorylated at site Y(685), a site previously found phosphorylated upon VEGF challenge, via Src activation. In vitro experiments showed that VEGF-induced VE-cadherin phosphorylation, preceded the cleavage of its extracellular adhesive domain (sVE, 90 kDa). Interestingly, metalloproteases (MMPs) secreted by glioma cell lines were responsible for sVE release. Because VEGF and MMPs are important components of tumor microenvironment, we hypothesized that VE-cadherin proteolysis might occur in human brain tumors. Analysis of glioma patient sera prior treatment confirmed the presence of sVE in bloodstream. Furthermore, sVE levels studied in a cohort of 53 glioma patients were significantly predictive of the overall survival at three years (HR 0.13 [0.04; 0.40] p ≤ 0.001), irrespective to histopathological grade of tumors. Altogether, these results suggest that VE-cadherin structural modifications should be examined as candidate biomarkers of tumor vessel abnormalities, with promising applications in oncology.

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