Integrin avB3 acting as membrane receptor for thyroid hormones mediates angiogenesis in malignant T cells

Abstract: The interaction of lymphoid tumor cells with components of the extracellular matrix via integrin avb3 allows tumor survival and growth. This integrin was demonstrated to be the membrane receptor for thyroid hormones (THs) in several tissues. We found that THs, acting as soluble integrin av...

Descripción completa

Guardado en:
Detalles Bibliográficos
Autores principales: Cayrol, María Florencia, Díaz Flaqué, María Celeste, Tharu, Fernando, Yang, Shao Ning, Sterle, Helena Andrea, Bolontrade, Marcela, Amorós, Mariana, Isse, Blanca, Farías, Ricardo Norberto, Haelee, Ahn, Tian, Ye F., Tabbò, Fabrizio, Singh, Ankur, Inghirami, Giorgio, Cerchietti, Leandro, Cremaschi, Graciela A.
Formato: Artículo
Lenguaje:Inglés
Inglés
Publicado: American Society of Hematology 2019
Materias:
Acceso en línea:https://repositorio.uca.edu.ar/handle/123456789/1441
Aporte de:
Descripción
Sumario:Abstract: The interaction of lymphoid tumor cells with components of the extracellular matrix via integrin avb3 allows tumor survival and growth. This integrin was demonstrated to be the membrane receptor for thyroid hormones (THs) in several tissues. We found that THs, acting as soluble integrin avb3 ligands, activated growth-related signaling pathways in T-cell lymphomas (TCLs). Specifically, TH-activated avb3 integrin signaling promoted TCL proliferation and angiogenesis, in part, via the upregulation of vascular endothelial growth factor (VEGF). Consequently, genetic or pharmacologic inhibition of integrin avb3 decreased VEGF production and induced TCL cell death in vitro and in human xenograft models. In sum, weshowthat integrin avb3 transduces prosurvival signals into TCL nuclei, suggesting a novel mechanism for the endocrine modulation of TCL pathophysiology. Targeting this mechanism could constitute an effective and potentially low-toxicity chemotherapy-free treatment of TCL patients.