The Tumor Microenvironment and the Estrogen Loop in Thyroid Cancer
Nerina Denaro, Rebecca Romanò, Salvatore Alfieri, Alessia Dolci, Lisa Licitra, Imperia Nuzzolese, Michele Ghidini, Claudia Bareggi, Valentina Bertaglia, Cinzia Solinas, Ornella Garrone
Abstract
Thyroid cancer (TC) cells employ multiple signaling pathways, such as PI3K/AKT/mTOR and RAS/Raf/MAPK, fostering cell proliferation, survival and metastasis. Through a complex interplay with immune cells, inflammatory mediators and stroma, TC cells support an immunosuppressive, inflamed, pro-carcinogenic TME. Moreover, the participation of estrogens in TC pathogenesis has previously been hypothesized, in view of the higher TC incidence observed among females. In this respect, the interactions between estrogens and the TME in TC could represent a relevant, unexplored area of research. We thereby collectively reviewed the available evidence concerning the potential carcinogenic role of estrogens in TC, specifically focusing on their crosstalk with the TME.