Evidence for post-translational processing of vascular endothelial (VE)-cadherin in brain tumors: towards a candidate biomarker

PloS One
I VilgrainFrançois Berger

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 ≤ ...Continue Reading

References

Aug 18, 1999·Proceedings of the National Academy of Sciences of the United States of America·M CoradaE Dejana
Oct 3, 2002·Neuro-oncology·Margaret WrenschMitchel S Berger
Feb 14, 2003·The Journal of Biological Chemistry·Bastien HermantDanielle Gulino-Debrac
Jul 2, 2003·Nature Reviews. Cancer·Jasti S Rao
Jan 22, 2005·Current Opinion in Genetics & Development·Peter BalukDonald M McDonald
Jan 22, 2005·Circulation Research·Nathalie LambengPhilippe Huber
Mar 11, 2005·The New England Journal of Medicine·Roger StuppUNKNOWN National Cancer Institute of Canada Clinical Trials Group
Mar 26, 2005·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Hélène Hudry-ClergeonIsabelle Vilgrain
Apr 30, 2005·The EMBO Journal·Ulf BaumeisterDietmar Vestweber
Mar 24, 2006·Journal of Neuro-oncology·O KargiotisA P Kyritsis
May 30, 2006·Laboratory Investigation; a Journal of Technical Methods and Pathology·Janice A NagyHarold F Dvorak
Nov 10, 2006·Nature Reviews. Cancer·Emanuel F PetricoinLance A Liotta
Jul 10, 2007·Acta Neuropathologica·David N LouisPaul Kleihues
Jul 12, 2007·Nature Clinical Practice. Urology·Cora N Sternberg
Jul 24, 2007·Nature Reviews. Neuroscience·Rakesh K JainTracy T Batchelor
Jun 21, 2008·Journal of Cell Science·Elisabetta DejanaMaria Grazia Lampugnani
Mar 10, 2009·Current Opinion in Cell Biology·Tony Hunter
Jun 3, 2009·The Oncologist·Andrew S ChiTracy T Batchelor
Jun 18, 2010·Journal of Neuroradiology. Journal De Neuroradiologie·Z JiangA Krainik
Sep 24, 2010·Acta Neuropathologica·Ghazaleh TabatabaiMichael Weller
Jan 29, 2011·Journal of Molecular Biology·Julia BraschLawrence Shapiro
Mar 29, 2011·The Journal of Allergy and Clinical Immunology·Laurence BouilletIsabelle Vilgrain
Mar 30, 2011·Glia·Nikki A CharlesHelmut Kettenmann
May 20, 2011·Nature·Peter Carmeliet, Rakesh K Jain

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Citations

Sep 23, 2014·Future Oncology·Cristiana TanaseMonica Neagu
May 27, 2014·American Journal of Physiology. Heart and Circulatory Physiology·Adama SidibéIsabelle Vilgrain
Dec 3, 2016·Biochemistry. Biokhimii︠a︡·I I GalkinE N Popova
Jan 28, 2021·Immunological Investigations·Yeping LuoZuocheng Yang

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Datasets Mentioned

BETA
GM6001

Methods Mentioned

BETA
protein assay
immunoprecipitation
Assay
biopsy
surgical resections
zymography
glycosylation
ELISA

Software Mentioned

ImageJ
Stata
NIH Image J

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