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Evidence for post-translational processing of vascular endothelial (VE)-cadherin in brain tumors: towards a candidate biomarker.
Vilgrain, Isabelle; Sidibé, Adama; Polena, Helena; Cand, Francine; Mannic, Tiphaine; Arboleas, Mélanie; Boccard, Sandra; Baudet, Antoine; Gulino-Debrac, Danielle; Bouillet, Laurence; Quesada, Jean-Louis; Mendoza, Christophe; Lebas, Jean-François; Pelletier, Laurent; Berger, François.
Afiliación
  • Vilgrain I; INSERM, Unit 1036, Biology of Cancer and Infection, Grenoble, France ; UJF-Grenoble 1, Biology of Cancer and Infection, Grenoble, France ; CEA, DSV/iRTSV, Biology of Cancer and Infection, Grenoble, France.
  • Sidibé A; INSERM, Unit 1036, Biology of Cancer and Infection, Grenoble, France ; UJF-Grenoble 1, Biology of Cancer and Infection, Grenoble, France ; CEA, DSV/iRTSV, Biology of Cancer and Infection, Grenoble, France.
  • Polena H; INSERM, Unit 1036, Biology of Cancer and Infection, Grenoble, France ; UJF-Grenoble 1, Biology of Cancer and Infection, Grenoble, France ; CEA, DSV/iRTSV, Biology of Cancer and Infection, Grenoble, France.
  • Cand F; INSERM, Unit 1036, Biology of Cancer and Infection, Grenoble, France ; UJF-Grenoble 1, Biology of Cancer and Infection, Grenoble, France ; CEA, DSV/iRTSV, Biology of Cancer and Infection, Grenoble, France.
  • Mannic T; INSERM, Unit 1036, Biology of Cancer and Infection, Grenoble, France ; UJF-Grenoble 1, Biology of Cancer and Infection, Grenoble, France ; CEA, DSV/iRTSV, Biology of Cancer and Infection, Grenoble, France.
  • Arboleas M; INSERM, Unit 1036, Biology of Cancer and Infection, Grenoble, France ; UJF-Grenoble 1, Biology of Cancer and Infection, Grenoble, France ; CEA, DSV/iRTSV, Biology of Cancer and Infection, Grenoble, France.
  • Boccard S; INSERM, Unit 1036, Biology of Cancer and Infection, Grenoble, France ; UJF-Grenoble 1, Biology of Cancer and Infection, Grenoble, France ; CEA, DSV/iRTSV, Biology of Cancer and Infection, Grenoble, France.
  • Baudet A; Grenoble University Hospital, Division of Internal Medicine, Grenoble, France.
  • Gulino-Debrac D; INSERM, Unit 1036, Biology of Cancer and Infection, Grenoble, France ; UJF-Grenoble 1, Biology of Cancer and Infection, Grenoble, France ; CEA, DSV/iRTSV, Biology of Cancer and Infection, Grenoble, France.
  • Bouillet L; INSERM, Unit 1036, Biology of Cancer and Infection, Grenoble, France ; UJF-Grenoble 1, Biology of Cancer and Infection, Grenoble, France ; CEA, DSV/iRTSV, Biology of Cancer and Infection, Grenoble, France ; Grenoble University Hospital, Division of Internal Medicine, Grenoble, France.
  • Quesada JL; INSERM 003, Clinical Investigation Center, Grenoble University Hospital, Grenoble, France.
  • Mendoza C; INSERM 003, Clinical Investigation Center, Grenoble University Hospital, Grenoble, France.
  • Lebas JF; Grenoble University Hospital, Division of Radiology, Grenoble, France.
  • Pelletier L; INSERM, Unit 836 Brain Nanomedicine, Grenoble Neurosciences Institut Grenoble, Grenoble, France ; Joseph Fourier University, Medicine School, Saint-Martin-d'Hères, France ; Grenoble University Hospital, Biology and Pathology Institute, Grenoble, France.
  • Berger F; INSERM, Unit 836 Brain Nanomedicine, Grenoble Neurosciences Institut Grenoble, Grenoble, France ; Joseph Fourier University, Medicine School, Saint-Martin-d'Hères, France ; Grenoble University Hospital, Division of Oncology, Grenoble, France.
PLoS One ; 8(12): e80056, 2013.
Article en En | MEDLINE | ID: mdl-24358106
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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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Encefálicas / Biomarcadores de Tumor / Antígenos CD / Cadherinas / Glioma Límite: Adult / Aged / Female / Humans / Male / Middle aged Idioma: En Revista: PLoS One Asunto de la revista: CIENCIA / MEDICINA Año: 2013 Tipo del documento: Article País de afiliación: Francia Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Encefálicas / Biomarcadores de Tumor / Antígenos CD / Cadherinas / Glioma Límite: Adult / Aged / Female / Humans / Male / Middle aged Idioma: En Revista: PLoS One Asunto de la revista: CIENCIA / MEDICINA Año: 2013 Tipo del documento: Article País de afiliación: Francia Pais de publicación: Estados Unidos