Pharmaceutical Research Institute, Albany College of Pharmacy and Health Sciences, Rensselear, NY, United States.
Department of Radiation Oncology, The Cleveland Clinic, Cleveland, OH, United States.
Front Endocrinol (Lausanne). 2021 Jun 21;12:691736. doi: 10.3389/fendo.2021.691736. eCollection 2021.
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. studies have shown that tetraiodothyroacetic acid (tetrac), a derivative of T4, acts 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 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.
左甲状腺素（T4）是整合素αvβ3细胞外结构域上甲状腺激素类似物受体的主要配体。整合素在癌细胞、快速分裂的内皮细胞和血小板中过度表达和激活。其生物学结果是，在生理浓度下且不转化为 3,3',5-三碘-L-甲状腺素（T3）的 T4 可能刺激癌细胞增殖和与癌症相关的血管生成和血小板凝结。T4 对血小板的促血栓形成活性被假设为支持与癌症相关的血液凝结，并有助于肿瘤细胞转移。我们检查了其中一些发现，因为它们可能与甲状腺癌有关。分化型甲状腺癌细胞对生理水平的 T4 反应增加，增殖增加。因此，在 T4 给药和随之而来的内源性促甲状腺激素抑制未能阻止疾病的分化型甲状腺癌患者中，T4 治疗可能刺激肿瘤细胞增殖的可能性是存在的。研究表明，四碘甲状腺原氨酸乙酸（tetrac），一种 T4 的衍生物，作用于整合素以阻断 T4 对甲状腺癌和其他实体肿瘤细胞的支持。T4 和 tetrac 或化学修饰的 tetrac 的作用调节甲状腺癌细胞中的基因表达。T4 诱导放射性抗性 通过在各种癌细胞中的整合素诱导构象变化，尽管尚未在甲状腺癌细胞中建立。整合素αvβ3 上的甲状腺激素受体介导 T4 对分化型甲状腺癌细胞的许多作用，这些作用支持癌症的生物学。需要进一步研究以确定 T4 是否作用于甲状腺癌细胞。
