Inhibiting endothelin receptors with macitentan strengthens the bone protective action of RANKL inhibition and reduces metastatic dissemination in osteosarcoma

Autor: Javier Muñoz-Garcia, Jorge William Vargas-Franco, Bénédicte Brounais-Le Royer, Denis Cochonneau, Jérôme Amiaud, Marie-Françoise Heymann, Dominique Heymann, Frédéric Lézot
Přispěvatelé: Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER, Universidad de Antioquia = University of Antioquia [Medellín, Colombia], Nantes Université (Nantes Univ), Unité de fonctionnalité et ingénierie de protéines (UFIP), Centre National de la Recherche Scientifique (CNRS)-Nantes université - UFR des Sciences et des Techniques (Nantes univ - UFR ST), Nantes Université - pôle Sciences et technologie, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Sciences et technologie, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), University of Sheffield [Sheffield], CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Maladies génétiques d'expression pédiatrique [CHU Trousseau] (Inserm U933), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Heymann, Dominique
Jazyk: angličtina
Rok vydání: 2022
Předmět:
[SDV.MHEP.EM] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism
musculoskeletal diseases
[SDV.MHEP.PED]Life Sciences [q-bio]/Human health and pathology/Pediatrics
[SDV.MHEP.AHA] Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO]
[SDV.MHEP.RSOA] Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system
Cancer Research
RANKL
bone protection
[SDV.CAN]Life Sciences [q-bio]/Cancer
[SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism
[SDV.BC.IC] Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB]
[SDV.MHEP.PED] Life Sciences [q-bio]/Human health and pathology/Pediatrics
[SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system
[SDV.CAN] Life Sciences [q-bio]/Cancer
Oncology
osteosarcoma
endothelin
metastases
[SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB]
[SDV.MHEP.AHA]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO]
Zdroj: Cancers; Volume 14; Issue 7; Pages: 1765
Cancers
Cancers, 2022, 14 (7), pp.1765. ⟨10.3390/cancers14071765⟩
ISSN: 2072-6694
DOI: 10.3390/cancers14071765⟩
Popis: International audience; Current treatments for osteosarcoma, combining conventional polychemotherapy and surgery, make it possible to attain a five-year survival rate of 70% in affected individuals. The presence of chemoresistance and metastases significantly shorten the patient’s lifespan, making identification of new therapeutic tools essential. Inhibiting bone resorption has been shown to be an efficient adjuvant strategy impacting the metastatic dissemination of osteosarcoma, tumor growth, and associated bone destruction. Unfortunately, over-apposition of mineralized matrix by normal and tumoral osteoblasts was associated with this inhibition. Endothelin signaling is implicated in the functional differentiation of osteoblasts, raising the question of the potential value of inhibiting it alone, or in combination with bone resorption repression. Using mouse models of osteosarcoma, the impact of macitentan, an endothelin receptor inhibitor, was evaluated regarding tumor growth, metastatic dissemination, matrix over-apposition secondary to RANKL blockade, and safety when combined with chemotherapy. The results showed that macitentan has no impact on tumor growth or sensitivity to ifosfamide, but significantly reduces tumoral osteoid tissue formation and the metastatic capacity of the osteosarcoma. To conclude, macitentan appears to be a promising therapeutic adjuvant for osteosarcoma alone or associated with bone resorption inhibitors.
Databáze: OpenAIRE
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