THYROID HORMONES INFLUENCE METASTATIC AND NON-METASTATIC MELANOMA PROGRESSION

CAYROL F; STERLE HA; DEBERNARDI MM; GONZALEZ G; DIAZ ALBUJA, JA; CAMPOS HAEDO MN; CREMASCHI GA

Congreso; REUNIÓN DE SOCIEDADES DE BIOCIENCIAS 2022; 2022

Thyroid hormones (THs) can affect tumor behavior by direct actionson cancer cells through molecular pathways involved in tumorigen-esis, cancer metabolism, tumor proliferation/survival, invasiveness,and angiogenesis. To evaluate if THs can influence melanoma (ME)cell growth we first evaluated nuclear (TR) and membrane (integrinαVβ3) THs receptor levels in human (A375 and WM35) and mouse(B16F10 and B16F1) ME cells. We found transcriptional and proteinlevels of these receptors in all the ME cells analyzed. We also evalu-ated THs effect on ME cell proliferation and found that physiologicaland supraphysiological levels of these hormones induce 15 to 40%ME cell proliferation (p<0.05); and that this effect is reduced by thepharmacological inhibition of integrin αVβ3 (p<0.05). Importantly, wefound expression of αV and β3 integrins in ME patient samples fromthe TCGA-SKCM project, suggesting that the membrane receptorfor THs can be a possible target to improve ME therapy. Increasingevidence indicates that THs can also affect the composition of thetumor microenvironment and the immune responses, thus influenc-ing tumor progression. Therefore, we analyzed the effect of thyroidstatus on B16F10 and B16F1 in vivo syngeneic mouse models. Inboth models, hyperthyroid mice showed an increased tumor growthrate (p<0.05), but no significant effect of hypothyroidism on tumorgrowth has been observed. We also analyzed the distribution of im-mune cell subsets in spleens and tumor-draining lymph nodes fromthese animals and we observed that thyroid status affects the dis-tribution of cytotoxic CD8+ T cells, B lymphocytes, and myeloid-de-rived suppressor cells. Further experiments should be performed todetermine the effect of THs on the functionality of these cells. Ourresults indicate that THs can induce ME cell proliferation throughαvβ3 integrin and are also involved in the systemic anti-ME immuneresponse.