Non-genomic actions of thyroid hormones regulate the growth and angiogenesis of T cell lymphomas

• Autores: Cayrol, María Florencia; Sterle, Helena Andrea; Díaz Flaqué, María Celeste; Barreiro Arcos, María Laura; Cremaschi, Graciela A.
• Año de publicación: 2019
• Idioma: inglés
• Tipo de recurso: artículo
• Fuente: Frontiers in Endocrinology. 2019;10
• Materia: TUMORES; GLANDULA TIROIDES; HORMONAS; CANCER; ANGIOGENESIS
• Institución: Pontificia Universidad Católica Argentina

Fil: Cayrol, María Florencia. Pontificia Universidad Católica Argentina. Facultad de Ciencias Médicas. Instituto de Investigaciones Biomédicas; Argentina
Fil: Cayrol, María Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Sterle, Helena Andrea. Pontificia Universidad Católica Argentina. Facultad de Ciencias Médicas. Instituto de Investigaciones Biomédicas; Argentina
Fil: Sterle, Helena Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Díaz Flaqué, María Celeste. Pontificia Universidad Católica Argentina. Facultad de Ciencias Médicas. Instituto de Investigaciones Biomédicas; Argentina
Fil: Díaz Flaqué, María Celeste. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Barreiro Arcos, María Laura. Pontificia Universidad Católica Argentina. Facultad de Ciencias Médicas. Instituto de Investigaciones Biomédicas; Argentina
Fil: Barreiro Arcos, María Laura. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Cremaschi, Graciela A. Pontificia Universidad Católica Argentina. Facultad de Ciencias Médicas. Instituto de Investigaciones Biomédicas; Argentina
Fil: Cremaschi, Graciela A. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Cremaschi, Graciela A. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Laboratorio de Radioisotópos; Argentina
Abstract: T-cell lymphomas (TCL) are a heterogeneous group of aggressive clinical lymphoproliferative disorders with considerable clinical, morphological, immunophenotypic, and genetic variation, including ~10-15% of all lymphoid neoplasms. Several evidences indicate an important role of the non-neoplastic microenvironment in promoting both tumor growth and dissemination in T cell malignancies. Thus, dysregulation of integrin expression and activity is associated with TCL survival and proliferation. We found that thyroid hormones acting via the integrin αvβ3 receptor are crucial factors in tumor microenvironment (TME) affecting the pathophysiology of TCL cells. Specifically, TH-activated αvβ3 integrin signaling promoted TCL proliferation and induced and an angiogenic program via the up-regulation of the vascular endothelial growth factor (VEGF). This was observed both on different TCL cell lines representing the different subtypes of human hematological malignancy, and in preclinical models of TCL tumors xenotransplanted in immunodeficient mice as well. Moreover, development of solid tumors by inoculation of murine TCLs in syngeneic hyperthyroid mice, showed increased tumor growth along with increased expression of cell cycle regulators. The genomic or pharmacological inhibition of integrin αvβ3 decreased VEGF production, induced TCL cell death and decreased in vivo tumor growth and angiogenesis. Here, we review the non-genomic actions of THs on TCL regulation and their contribution to TCL development and evolution. These actions not only provide novel new insights on the endocrine modulation of TCL, but also provide a potential molecular target for its treatment.