Evidence for post-translational processing of vascular endothelial (VE)-cadherin in brain tumors: towards a candidate biomarker
| العنوان: | Evidence for post-translational processing of vascular endothelial (VE)-cadherin in brain tumors: towards a candidate biomarker |
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| المؤلفون: | Tiphaine Mannic, Francine Cand, Laurent Pelletier, Mélanie Arboleas, Jean-Louis Quesada, Jean-Francois LeBas, Christophe Mendoza, Laurence Bouillet, Isabelle Vilgrain, Danielle Gulino-Debrac, François Berger, Sandra Boccard, Adama Sidibé, Helena Polena, Antoine Baudet |
| المصدر: | PLoS ONE, Vol 8, Iss 12, p e80056 (2013) Europe PubMed Central PLoS ONE |
| بيانات النشر: | Public Library of Science (PLoS), 2013. |
| سنة النشر: | 2013 |
| مصطلحات موضوعية: | Adult, Male, Pathology, medicine.medical_specialty, Endothelium, lcsh:Medicine, chemistry.chemical_compound, Young Adult, Antigens, CD, Glioma, medicine, Biomarkers, Tumor, Human Umbilical Vein Endothelial Cells, Tumor Microenvironment, Humans, Phosphorylation, lcsh:Science, Aged, Tumor microenvironment, Multidisciplinary, Chemistry, Cadherin, Brain Neoplasms, lcsh:R, Endothelial Cells, Tyrosine phosphorylation, Middle Aged, medicine.disease, Cadherins, medicine.anatomical_structure, Female, lcsh:Q, Endothelium, Vascular, VE-cadherin, Proto-oncogene tyrosine-protein kinase Src, Research Article |
| الوصف: | 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. |
| اللغة: | English |
| تدمد: | 1932-6203 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::c2da5ba69b4e7a90ec556f5ca186acc5 http://europepmc.org/articles/PMC3864785?pdf=render |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....c2da5ba69b4e7a90ec556f5ca186acc5 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19326203 |
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