Matricellular TSP-1 as a target of interest for impeding melanoma spreading: towards a therapeutic use for TAX2 peptide
| العنوان: | Matricellular TSP-1 as a target of interest for impeding melanoma spreading: towards a therapeutic use for TAX2 peptide |
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| المؤلفون: | Jérôme Devy, Caroline Fichel, Marie-Danièle Diebold, Camille Boulagnon-Rombi, Stéphane Dedieu, Louis Theret, Christophe Schneider, Albin Jeanne, Nicole Bouland, Laurent Martiny |
| المساهمون: | Matrice extracellulaire et dynamique cellulaire - UMR 7369 (MEDyC), 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)-Université de Reims Champagne-Ardenne (URCA)-Centre National de la Recherche Scientifique (CNRS), Hôpital universitaire Robert Debré [Reims], Laboratoire d'Anatomopathologie, Centre hospitalier Universitaire, Laboratoire de Signalisation et Récepteurs Matriciels (SiRMa), Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Université de Reims Champagne-Ardenne (URCA)-Centre National de la Recherche Scientifique (CNRS)-SFR CAP Santé (Champagne-Ardenne Picardie Santé), AJ was recipient of grants from the Ministère de l’Enseignement Supérieur et de la Recherche (2010-2013)., The authors acknowledge supports from Centre National de la Recherche Scientifique (CNRS), Région Champagne-Ardenne and SATT Nord, The authors acknowledge A. Thomachot for editorial assistance. |
| المصدر: | Clinical and Experimental Metastasis Clinical and Experimental Metastasis, Springer Verlag, 2017, 33 (7), pp.637-649. ⟨10.1007/s10585-016-9803-0⟩ |
| سنة النشر: | 2016 |
| مصطلحات موضوعية: | 0301 basic medicine, Cancer Research, medicine.medical_specialty, Stromal cell, Lung Neoplasms, Skin Neoplasms, Melanoma, Experimental, CD47 Antigen, Peptides, Cyclic, Metastasis, Thrombospondin 1, 03 medical and health sciences, Mice, 0302 clinical medicine, Surgical oncology, Internal medicine, Cell Line, Tumor, medicine, Animals, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Neoplasm Metastasis, CD47, Melanoma, Tumor microenvironment, Hematology, Neovascularization, Pathologic, business.industry, TAX2 peptide, General Medicine, medicine.disease, Innovative therapeutic strategy, Xenograft Model Antitumor Assays, 3. Good health, 030104 developmental biology, Oncology, 030220 oncology & carcinogenesis, Cancer research, business, Thrombospondin-1 |
| الوصف: | International audience; Thrombospondin-1 (TSP-1) is a matricellular glycoprotein known for being highly expressed within a tumor microenvironment, where it promotes an aggressive phenotype particularly by interacting with the CD47 cell-surface receptor. While it originates from the stromal compartment in many malignancies, melanoma is an exception as invasive and metastatic melanoma cells overexpress TSP-1. We recently demonstrated that a new molecular agent that selectively prevents TSP-1 binding to CD47, called TAX2, exhibits anti-cancer properties when administered systemically by decreasing viable tumor tissue within subcutaneous B16 melanoma allografts. At the same time, emerging evidence was published suggesting a contribution of TSP-1 in melanoma metastatic dissemination and resistance to treatment. Through a comprehensive systems biology approach based on multiple genomics and proteomics databases analyses, we first identified a TSP-1-centered interaction network that is overexpressed in metastatic melanoma. Then, we investigated the effects of disrupting TSP-1:CD47 interaction in A375 human malignant melanoma xenografts. In this model, TAX2 systemic administrations induce tumor necrosis by decreasing intra-tumoral blood flow, while concomitantly making tumors less infiltrative. Besides, TAX2 treatment also drastically inhibits B16F10 murine melanoma cells metastatic dissemination and growth in a syngeneic experimental model of lung metastasis, as demonstrated by histopathological analyses as well as longitudinal and quantitative µCT follow-up of metastatic progression. Altogether, the results obtained by combining bioinformatics and preclinical studies strongly suggest that targeting TSP-1/CD47 axis may represent a valuable therapeutic alternative for hampering melanoma spreading. |
| تدمد: | 1573-7276 0262-0898 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::3cfd3196dd10c1c49ee5b3f418749036 https://pubmed.ncbi.nlm.nih.gov/27349907 |
| حقوق: | CLOSED |
| رقم الأكسشن: | edsair.doi.dedup.....3cfd3196dd10c1c49ee5b3f418749036 |
| قاعدة البيانات: | OpenAIRE |
Find this article in full text from Springer Verlag. | تدمد: | 15737276 02620898 |
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