INHIBITION OF THE INTEGRIN ALPHA-V BETA-3 REVERTS THE PARADOXICAL EFFECT OF LEVOTHYROXINE REPLACEMENT DURING BEXAROTENE THERAPY IN CUTANEOUS T-CELL LYMPHOMA (CTCL)

REVUELTA, V; DÍAZ FLAQUÉ, MARÍA CELESTE; CREMASCHI, G; CAYROL, FLORENCIA; PAULAZO, M.A.; ROSEMBLIT, CINTHIA; DEBERNARDI, M; STERLE, HELENA ANDREA; CERCHIETTI L

Mar del plata

Congreso; Reunion conjunta SAIC SAI SAFIS; 2018

Bexarotene (Bex), a RXR agonist used for CTCL treatment, causes hypothyroidism in more than 90% of patients, thus requiring the concomitant administration of levothyroxine (T4). We found that physiological levels of thyroid hormones (TH) contribute to the malignant phenotype of CTCL by activating TH membrane receptor (mTR), the integrin αVβ3. Using RNA-sequencing and qPCR assays in Bex-treated HuT78 CTCL cells we found that Bex induces transcriptional and biological changes related to decreased cell proliferation and chemotaxis, as well as increased proliferation and interferon response. Lack of TH supplementation increased apoptosis and decreased proliferation of CTCL cells in vitro. Also, we studied the impact of T4 addition to Bex treatment (BexT4+) in mice bearing a syngeneic TCL solid tumor and found that Bex decreased tumor growth (p