Thyroid hormones (THs) induce oncogenic signaling pathways involved in T cell lymphoma (TCL) progression

DEBERNARDI MM; DIAZ ALBUJA, JA; STERLE H; PAULAZO A; DIAZ FLAQUÉ MC; ROSEMBLIT C; CREMASCHI GA; CAYROL F

Congreso; SAFIS-ALACF 2021; 2021

THs influences tumor progression by direct actions on cancer cells, tumor microenvironment and the antitumor immunity. Ourmost recent results indicate that THs, acting via integrin αVβ3, promotes cell proliferation, survival and induces an angiogenicprogram in TCL cells. These lymphoproliferative disorders are very aggressive, and the available therapeutic regimens have poorresults, with a high rate of relapses and few effective options for rescue therapy. The understanding of the molecular mechanismsof THs actions in malignant cells could lead to the identification of new therapeutic targets.The main aim of this work was to evaluate the effect of THs on the oncogenic intracellular pathways that influence lymphomaprogression and were found dysregulated in most of TCL patients. For this propose we analyzed TCL cell lines corresponding toimmature (CUTLL1) and mature (OCI-Ly12, OCI-Ly13.2) human subtypes after 10, 15 and 30 minutes THs treatment. We foundthat physiological concentrations of THs significantly increase STAT1, 3 and 5 phosphorylation in both CUTLL1 and LY13.2 (p<0.05,n=3) TCL cells. Moreover, cilengitide, a specific inhibitor of integrin αVβ3, significantly decreases not only the total effect of THson STAT1 and 3 phosphorylation but also reduce the basal activation of these transcription factors (p<0.05, n=3) in TCL cells. Onthe other hand, it was found that the genetic program related to GATA3 transcription factor was associated with a poor clinicalresponse in TCL patients. We thus, evaluate GATA3 expression after 48 hours treatment with THs and found a significant increasein the TCL cells evaluated (p<0.05, n=3). All data are shown as mean ± SD.Our results provide the rational basis to continue studying the molecular mechanisms of THs actions in malignant cells that couldlead to the identification of new therapeutic targets, like integrin αVβ3, to improve current treatment outcomes in TCL patients