Targeting RAGE prevents muscle wasting and prolongs survival in cancer cachexia
| العنوان: | Targeting RAGE prevents muscle wasting and prolongs survival in cancer cachexia |
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| المؤلفون: | Renzini, Alessandra, Marroncelli, Nicoletta, Cavioli, Giorgia, Di Francescantonio, Silvia, Forcina, Laura, Lambridis, Alessandro, Di Giorgio, Eros, Valente, Sergio, Mai, Antonello, Giampietri, Claudia, Magenta, Alessandra, de Santa, Francesca, Adamo, Sergio, Coletti, Dario, Moresi, Viviana |
| المساهمون: | Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome] (UNIROMA), Università degli Studi di Udine - University of Udine [Italie], Department of Drug Chemistry and Technologies = Dipartimento di Chimica et Tecnologie del Farmaco [Roma], Institut Pasteur, Fondation Cenci Bolognetti - Istituto Pasteur Italia, Fondazione Cenci Bolognetti, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome] (UNIROMA), Department of Anatomy, Histology, Forensic Medicine and Orthopedic [Roma] (DAHFMO), Department of Molecular Medicine, National Research Council (CNR), Adaptation Biologique et Vieillissement = Biological Adaptation and Ageing (B2A), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), COLETTI, DARIO |
| المصدر: | Journal of Cachexia, Sarcopenia and Muscle Journal of Cachexia, Sarcopenia and Muscle, 2020, 11 (4), pp.929-946. ⟨10.1002/jcsm.12561⟩ Journal of Cachexia, Sarcopenia and Muscle, Vol 11, Iss 4, Pp 929-946 (2020) |
| بيانات النشر: | HAL CCSD, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | 0301 basic medicine, lcsh:Diseases of the musculoskeletal system, Cachexia, Receptor for Advanced Glycation End Products, S100B, Muscle necroptosis, RAGE (receptor), Mice, 0302 clinical medicine, Neoplasms, Satellite cells, Orthopedics and Sports Medicine, HMGB1, cancer cachexia, cytokines, inflammation, muscle atrophy, myogenin, RAGE, biology, Myogenesis, HDACi, Cancer cachexia, lcsh:Human anatomy, Membrane repair mechanism, Muscle atrophy, 030220 oncology & carcinogenesis, Cytokines, Original Article, Tumor necrosis factor alpha, Myogenin, medicine.symptom, Duchenne muscular dystrophy, Inflammation, [SDV.CAN]Life Sciences [q-bio]/Cancer, lcsh:QM1-695, Proinflammatory cytokine, 03 medical and health sciences, [SDV.CAN] Life Sciences [q-bio]/Cancer, Physiology (medical), medicine, Animals, Humans, business.industry, HDAC4, Original Articles, medicine.disease, 030104 developmental biology, Cancer research, biology.protein, lcsh:RC925-935, business |
| الوصف: | International audience; Background Cachexia, a multifactorial syndrome affecting more than 50% of patients with advanced cancer and responsible for ~20% of cancer-associated deaths, is still a poorly understood process without a standard cure available. Skeletal muscle atrophy caused by systemic inflammation is a major clinical feature of cachexia, leading to weight loss, dampening patients' quality of life, and reducing patients' response to anticancer therapy. RAGE (receptor for advanced glycation end-products) is a multiligand receptor of the immunoglobulin superfamily and a mediator of muscle regeneration, inflammation, and cancer. Methods By using murine models consisting in the injection of colon 26 murine adenocarcinoma (C26-ADK) or Lewis lung carcinoma (LLC) cells in BALB/c and C57BL/6 or Ager À/À (RAGE-null) mice, respectively, we investigated the involvement of RAGE signalling in the main features of cancer cachexia, including the inflammatory state. In vitro experiments were performed using myotubes derived from C2C12 myoblasts or primary myoblasts isolated from C57BL/6 wild type and Ager À/À mice treated with the RAGE ligand, S100B (S100 calcium-binding protein B), TNF (tumor necrosis factor)α±IFN (interferon) γ, and tumour cell-or masses-conditioned media to analyse hallmarks of muscle atrophy. Finally, muscles of wild type and Ager À/ À mice were injected with TNFα/IFNγ or S100B in a tumour-free environment. Results We demonstrate that RAGE is determinant to activate signalling pathways leading to muscle protein degradation in the presence of proinflammatory cytokines and/or tumour-derived cachexia-inducing factors. We identify the RAGE ligand, S100B, as a novel factor able to induce muscle atrophy per se via a p38 MAPK (p38 mitogen-activated protein kinase)/myogenin axis and STAT3 (signal transducer and activator of transcription 3)-dependent MyoD (myoblast determination protein 1) degradation. Lastly, we found that in cancer conditions, an increase in serum levels of tumour-derived S100B and HMGB1 (high mobility group box 1) occurs leading to chronic activation/overexpression of RAGE, which induces hallmarks of cancer cachexia (i.e. muscle wasting, systemic inflammation, and release of tumour-derived pro-cachectic factors). Absence of RAGE in mice translates into reduced serum levels of cachexia-inducing factors, delayed loss of muscle mass and strength, reduced tumour progression, and increased survival. Conclusions RAGE is a molecular determinant in inducing the hallmarks of cancer cachexia, and molecular targeting of RAGE might represent a therapeutic strategy to prevent or counteract the cachectic syndrome. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 2190-5991 2190-6009 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::f4efc42355b35821fccb03e279418345 https://hal.sorbonne-universite.fr/hal-03714907 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....f4efc42355b35821fccb03e279418345 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 21905991 21906009 |
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