Non-genomic Actions of Thyroid Hormones Regulate the Growth and Angiogenesis of T Cell Lymphomas

CAYROL, FLORENCIA; STERLE, HELENA A.; DÍAZ FLAQUÉ, MARIA CELESTE; BARREIRO ARCOS, MARIA LAURA; CREMASCHI, GRACIELA A.

Frontiers in Endocrinology

Frontiers research foundation

Año: 2019 vol. 10

T-cell lymphomas (TCL) are a heterogeneous group of aggressive clinicallymphoproliferative disorders with considerable clinical, morphological,immunophenotypic, and genetic variation, including 10?15% of all lymphoidneoplasms. Several evidences indicate an important role of the non-neoplasticmicroenvironment in promoting both tumor growth and dissemination in T cellmalignancies. Thus, dysregulation of integrin expression and activity is associatedwith TCL survival and proliferation. We found that thyroid hormones acting via theintegrin avb3 receptor are crucial factors in tumor microenvironment (TME) affecting thepathophysiology of TCL cells. Specifically, TH-activated avb3 integrin signaling promotedTCL proliferation and induced and an angiogenic program via the up-regulation of thevascular endothelial growth factor (VEGF). This was observed both on different TCL celllines representing the different subtypes of human hematological malignancy, and inpreclinical models of TCL tumors xenotransplanted in immunodeficient mice as well.Moreover, development of solid tumors by inoculation of murine TCLs in syngeneichyperthyroid mice, showed increased tumor growth along with increased expressionof cell cycle regulators. The genomic or pharmacological inhibition of integrin avb3decreased VEGF production, induced TCL cell death and decreased in vivo tumorgrowth and angiogenesis. Here, we review the non-genomic actions of THs on TCLregulation and their contribution to TCL development and evolution. These actions notonly provide novel new insights on the endocrine modulation of TCL, but also provide apotential molecular target for its treatment.