1. Actions of Thyroid Hormones on Thyroid Cancers.
- Author
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Mousa SA, Hercbergs A, Lin HY, Keating KA, and Davis PJ
- Subjects
- Adenosine Triphosphate metabolism, B7-H1 Antigen metabolism, Gene Expression Regulation, Neoplastic, Humans, Integrin alphaVbeta3 metabolism, Programmed Cell Death 1 Receptor metabolism, Thyroid Neoplasms genetics, Thyroid Neoplasms metabolism, Thyroid Neoplasms pathology, Thyroid Hormones metabolism
- Abstract
L-Thyroxine (T4) is the principal ligand of the thyroid hormone analogue receptor on the extracellular domain of integrin αvβ3. The integrin is overexpressed and activated in cancer cells, rapidly dividing endothelial cells, and platelets. The biologic result is that T4 at physiological concentration and without conversion to 3,3',5-triiodo-L-thyronine (T3) may stimulate cancer cell proliferation and cancer-relevant angiogenesis and platelet coagulation. Pro-thrombotic activity of T4 on platelets is postulated to support cancer-linked blood clotting and to contribute to tumor cell metastasis. We examine some of these findings as they may relate to cancers of the thyroid. Differentiated thyroid cancer cells respond to physiological levels of T4 with increased proliferation. Thus, the possibility exists that in patients with differentiated thyroid carcinomas in whom T4 administration and consequent endogenous thyrotropin suppression have failed to arrest the disease, T4 treatment may be stimulating tumor cell proliferation. In vitro studies have shown that tetraiodothyroacetic acid (tetrac), a derivative of T4, acts via the integrin to block T4 support of thyroid cancer and other solid tumor cells. Actions of T4 and tetrac or chemically modified tetrac modulate gene expression in thyroid cancer cells. T4 induces radioresistance via induction of a conformational change in the integrin in various cancer cells, although not yet established in thyroid cancer cells. The thyroid hormone receptor on integrin αvβ3 mediates a number of actions of T4 on differentiated thyroid cancer cells that support the biology of the cancer. Additional studies are required to determine whether T4 acts on thyroid cancer cells., Competing Interests: SM and PD are the founders of NanoPharmaceuticals LLC, that is developing chemically modified forms of tetrac for application to management of various types of cancer, and PD is Chief Scientific Officer at the company. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Mousa, Hercbergs, Lin, Keating and Davis.)
- Published
- 2021
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