title: Thyroid hormones and their membrane receptors as therapeutic targets for T cell lymphomas.
abstract: Thyroid hormones (THs) are important regulators of metabolism, differentiation and cell proliferation. They can modify the physiology of human and murine T cell lymphomas (TCL). These effects involve genomic mechanisms, mediated by specific nuclear receptors (TR), as well as nongenomic mechanisms, that lead to the activation of different signaling pathways through the activation of a membrane receptor, the integrin αvβ3. Therefore, THs are able to induce the survival and growth of TCL. Specifically, the signaling induced by THs through the integrin αvβ3 activates proliferative and angiogenic programs, mediated by the regulation of the vascular endothelial growth factor (VEGF). The genomic or pharmacologic inhibition of integrin αvβ3 reduces the production of VEGF and induces cell death both in vitro and in xenograft models of human TCL. Here we review the mechanisms involved in the modulation of the physiology of TCL induced by THs, the analysis of the interaction between genomic and nongenomic actions of THs and their contribution to T cell lymphomagenesis. These actions of THs suggest a novel mechanism for the endocrine modulation of the physiopathology of TCL and they provide a potential molecular target for its treatment.
authors: Instituto de Investigaciones Biomédicas (BIOMED), Facultad de Ciencias Médicas, Pontificia Universidad Católica Argentina (UCA), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina; Laboratorio de Radioisótopos, Facultad de Farmacia y Bioquímica (FFyB), UBA, Buenos Aires, Argentina. Electronic address: graciela_cremaschi@uca.edu.ar.
authors: Graciela A
authors: GA
authors: Cremaschi
authors: Instituto de Investigaciones Biomédicas (BIOMED), Facultad de Ciencias Médicas, Pontificia Universidad Católica Argentina (UCA), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina.
authors: Florencia
authors: F
authors: Cayrol
authors: Instituto de Investigaciones Biomédicas (BIOMED), Facultad de Ciencias Médicas, Pontificia Universidad Católica Argentina (UCA), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina.
authors: Helena Andrea
authors: HA
authors: Sterle
authors: Instituto de Investigaciones Biomédicas (BIOMED), Facultad de Ciencias Médicas, Pontificia Universidad Católica Argentina (UCA), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina.
authors: María Celeste
authors: MC
authors: Díaz Flaqué
authors: Instituto de Investigaciones Biomédicas (BIOMED), Facultad de Ciencias Médicas, Pontificia Universidad Católica Argentina (UCA), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina; Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales (FCEyN), Universidad de Buenos Aires (UBA), Buenos Aires, Argentina.
authors: María Laura
authors: ML
authors: Barreiro Arcos
mesh_terms: D000818:Animals; D023281:Genomics; D006801:Humans; D016399:Lymphoma, T-Cell / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D011988:Receptors, Thyroid Hormone / Q000378:metabolism*; D013601:T-Lymphocytes / Q000378:metabolism; D013963:Thyroid Hormones / Q000378:metabolism*
chemical_list: D011988:Receptors, Thyroid Hormone; D013963:Thyroid Hormones
keywords: Angiogenesis; Integrin αvβ3; Proliferation; T cell lymphoma; Thyroid hormones