Integrin αvβ3 acting as membrane receptor for thyroid hormones mediates angiogenesis in malignant T cells

The interaction of lymphoid tumor cells with components of the extracellular matrix via integrin αvβ3 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 αvβ3 ligands...

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Detalles Bibliográficos
Autores: Cayrol, Maria Florencia, Díaz Flaqué, María Celeste, Tharu, Fernando, Yang, Shao Ning, Sterle, Helena Andrea, Bolontrade, Marcela Fabiana, Amorós, Mariana Andrea, Isse, Blanca Alicia de Los Angeles G., Farias, Ricardo Norberto, Ahn, Haelee, Tian, Ye F., Tabbò, Fabrizio, Singh, Ajnesh, Inghirami, Giorgio, Cerchietti, Leandro, Cremaschi, Graciela Alicia
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2015
País:Argentina
Institución:Consejo Nacional de Investigaciones Científicas y Técnicas
Repositorio:CONICET Digital (CONICET)
Idioma:inglés
OAI Identifier:oai:ri.conicet.gov.ar:11336/37796
Acceso en línea:http://hdl.handle.net/11336/37796
Access Level:acceso abierto
Palabra clave:Lymphoid Tumor Cells
Integrin Αvβ3
Tcl Proliferation
Endocrine Modulation
https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
Descripción
Sumario:The interaction of lymphoid tumor cells with components of the extracellular matrix via integrin αvβ3 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 αvβ3 ligands, activated growth-related signaling pathways in T-cell lymphomas (TCLs). Specifically, TH-activated αvβ3 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 αvβ3 decreased VEGF production and induced TCL cell death in vitro and in human xenograft models. In sum, we show that integrin αvβ3 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.

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