Identification of TAX2 peptide as a new unpredicted anti-cancer agent
| العنوان: | Identification of TAX2 peptide as a new unpredicted anti-cancer agent |
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| المؤلفون: | Christophe Schneider, Camille Boulagnon-Rombi, Albin Jeanne, Nicolas Floquet, Laurent Martiny, Marie-Danièle Diebold, Manuel Dauchez, Emilie Sick, Jérôme Devy, Louis Theret, Nicolas Belloy, Stéphane Dedieu |
| المساهمون: | Laboratoire de Biophotonique et Pharmacologie - UMR 7213 (LBP), Centre National de la Recherche Scientifique (CNRS)-Réseau nanophotonique et optique, Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA)), Matrice extracellulaire et dynamique cellulaire - UMR 7369 (MEDyC), Université de Reims Champagne-Ardenne (URCA)-SFR CAP Santé (Champagne-Ardenne Picardie Santé), Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Centre National de la Recherche Scientifique (CNRS) |
| المصدر: | Oncotarget Oncotarget, Impact journals, 2015, 6, pp.17981-18000. ⟨10.18632/oncotarget.4025⟩ Europe PubMed Central |
| بيانات النشر: | HAL CCSD, 2015. |
| سنة النشر: | 2015 |
| مصطلحات موضوعية: | CD36 Antigens, Time Factors, Angiogenesis, VEGF receptors, [SDV]Life Sciences [q-bio], Melanoma, Experimental, Angiogenesis Inhibitors, Tumor vascularization, Thrombospondin 1, angiogenesis, 0302 clinical medicine, Cell Movement, Medicine, Molecular Targeted Therapy, CD47, ComputingMilieux_MISCELLANEOUS, Mice, Inbred BALB C, 0303 health sciences, Neovascularization, Pathologic, biology, Magnetic Resonance Imaging, Tumor Burden, 3. Good health, Molecular Docking Simulation, Oncology, 030220 oncology & carcinogenesis, Computer-Aided Design, Research Paper, Protein Binding, Signal Transduction, endocrine system, medicine.medical_specialty, Mice, Nude, Molecular Dynamics Simulation, Selective antagonist, Nitric Oxide, Transfection, Peptides, Cyclic, Necrosis, 03 medical and health sciences, Cell Line, Tumor, Human Umbilical Vein Endothelial Cells, TSP-1, cancer, Animals, Humans, Pancreatic carcinoma, Cell Proliferation, 030304 developmental biology, Multimodal imaging, Tumor microenvironment, business.industry, Carcinoma, Physiological Angiogenesis, X-Ray Microtomography, Vascular Endothelial Growth Factor Receptor-2, Xenograft Model Antitumor Assays, Molecular biology, Surgery, Mice, Inbred C57BL, Pancreatic Neoplasms, Drug Design, biology.protein, CD36, Peptides, business |
| الوصف: | // Albin Jeanne 1, 2, 3 , Emilie Sick 1, 4 , Jerome Devy 1, 2 , Nicolas Floquet 5 , Nicolas Belloy 2, 6 , Louis Theret 1, 2 , Camille Boulagnon-Rombi 2, 7 , Marie-Daniele Diebold 2, 7 , Manuel Dauchez 2, 6 , Laurent Martiny 1, 2 , Christophe Schneider 1, 2 , Stephane Dedieu 1, 2 1 Universite de Reims Champagne-Ardenne, Laboratoire SiRMa, UFR Sciences Exactes et Naturelles, Reims, France 2 CNRS UMR 7369, Matrice Extracellulaire et Dynamique Cellulaire, MEDyC, Reims, France 3 SATT Nord, Lille, France 4 Universite de Strasbourg, CNRS UMR 7213, Illkirch, France 5 Institut des Biomolecules Max Mousseron (IBMM), CNRS UMR 5247, Universite de Montpellier, Ecole Normale Superieure de Chimie de Montpellier, Faculte de Pharmacie, Montpellier, France 6 Plateforme de Modelisation Moleculaire Multi-echelle (P3M), Universite de Reims Champagne-Ardenne, Reims, France 7 CHU de Reims, Laboratoire Central d’Anatomie et de Cytologie Pathologiques, Reims, France Correspondence to: Stephane Dedieu, e-mail: stephane.dedieu@univ-reims.fr Keywords: TSP-1, CD47, CD36, cancer, angiogenesis Received: March 24, 2015 Accepted: May 09, 2015 Published: May 22, 2015 ABSTRACT The multi-modular glycoprotein thrombospondin-1 (TSP-1) is considered as a key actor within the tumor microenvironment. Besides, TSP-1 binding to CD47 is widely reported to regulate cardiovascular function as it promotes vasoconstriction and angiogenesis limitation. Therefore, many studies focused on targeting TSP-1:CD47 interaction, aiming for up-regulation of physiological angiogenesis to enhance post-ischemia recovery or to facilitate engraftment. Thus, we sought to identify an innovative selective antagonist for TSP-1:CD47 interaction. Protein-protein docking and molecular dynamics simulations were conducted to design a novel CD47-derived peptide, called TAX2. TAX2 binds TSP-1 to prevent TSP-1:CD47 interaction, as revealed by ELISA and co-immunoprecipitation experiments. Unexpectedly, TAX2 inhibits in vitro and ex vivo angiogenesis features in a TSP-1-dependent manner. Consistently, our data highlighted that TAX2 promotes TSP-1 binding to CD36-containing complexes, leading to disruption of VEGFR2 activation and downstream NO signaling. Such unpredicted results prompted us to investigate TAX2 potential in tumor pathology. A multimodal imaging approach was conducted combining histopathological staining, MVD, MRI analysis and μCT monitoring for tumor angiography longitudinal follow-up and 3D quantification. TAX2 in vivo administrations highly disturb syngeneic melanoma tumor vascularization inducing extensive tumor necrosis and strongly inhibit growth rate and vascularization of human pancreatic carcinoma xenografts in nude mice. |
| اللغة: | English |
| تدمد: | 1949-2553 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::5724bcca061b701443c826fb45a424df https://hal.archives-ouvertes.fr/hal-01280451 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....5724bcca061b701443c826fb45a424df |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19492553 |
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