The Tumor Microenvironment and the Estrogen Loop in Thyroid Cancer
by
,
Nerina Denaro
1,*,†,
Rebecca Romanò
2,*,†,
Salvatore Alfieri
2,
Alessia Dolci
3,
Lisa Licitra
2,4,
Imperia Nuzzolese
2,
Michele Ghidini
1
,
Claudia Bareggi
1,
Valentina Bertaglia
5,
Cinzia Solinas
6 and
Ornella Garrone
1
1
Medical Oncology, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Ca’ Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy
2
Head and Neck Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 Milan, Italy
3
Endocrinology Unit, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Ca’ Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy
4
Department of Hematology and Oncology, University of Milan, 20122 Milan, Italy
5
Department of Oncology, University of Turin, S. Luigi Gonzaga Hospital, 10043 Orbassano, Italy
6
Medical Oncology, AOU Cagliari, Policlinico di Monserrato, 09042 Cagliari, Italy
*
Authors to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Cancers 2023, 15(9), 2458; https://doi.org/10.3390/cancers15092458
Submission received: 31 January 2023
/
Revised: 31 March 2023
/
Accepted: 20 April 2023
/
Published: 25 April 2023
(This article belongs to the Special Issue Advances in Understanding the Immune Network of Thyroid Cancers)
Simple Summary
The composite network of stromal, immune, vascular and cancer cells, which constitutes the tumor microenvironment (TME), has emerged as a player in thyroid cancer (TC) development and progression, as well as in several other cancer settings. In this context, estrogens may also contribute to TC carcinogenesis by activating proliferative pathways (namely PI3K/AKT/mTOR and RAS/Raf/MAPK), as well as by exerting immunosuppressive, pro-carcinogenic effects. To date, the complex interactions between the TME and estrogenic pathways have not been entirely unraveled in TC.
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.
