Actions of Thyroid Hormones on Thyroid Cancers

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.

Integrated analysis of circulating and tissue proteomes reveals that fibronectin 1 is a potential biomarker in papillary thyroid cancer

“…Integrative analyses revealed that integrin-mediated pathways are at the nexus of crosstalk between blood and tumor, and complement activation and coagulation cascades at the circulating level may promote tumor growth. This finding adds to recent discussions on the roles of thyroid hormones (THs) in thyroid cancer proliferation, metastasis, angiogenesis, and radio-resistance via integrin, which is overexpressed in cancer cells [ 40 ]. Additionally, the human complement system consists of approximately 50 serum proteins and membrane-bound regulators and receptors [ 41 ].…”

Association Between Genetic Risk, Adherence to Healthy Lifestyle Behavior, and Thyroid Cancer Risk

“…57,58 L-Thyroxine can stimulate cancer cell proliferation, cancerrelevant angiogenesis, and platelet coagulation. 59 Therefore, lifestyle and genetic factors may have a joint influence on TC by controlling the changes in thyroid hormones. In addition, the interaction between a high PRS and an unfavorable lifestyle showed no significance at an additive and multiplicative scale, which might partly be due to the relatively small sample size.…”

Prostate gland as a target organ of thyroid hormones: advances and controversies

“…T3 is an important regulator of androgen signaling, and more specific studies must be performed to discriminate between androgen-dependent and independent mechanisms. TH effects on cancer progression seem to be divergent and depend on the tumoral environment ( 51 , 75 ). As previously reviewed, THs exert dual actions.…”