title: Effect of the micronutrient iodine in thyroid carcinoma angiogenesis.
abstract: Iodide is a micronutrient essential for thyroid hormone production. The uptake and metabolism of iodide by thyrocytes is crucial to proper thyroid function. Iodide ions are drawn into the thyroid follicular cell via the sodium-iodide symporter (NIS) in the cell membrane and become integrated into tyrosyl residues to ultimately form thyroid hormones. We sought to learn how an abnormal concentration of iodide within thyrocyte can have significant effects on the thyroid, specifically the surrounding vascular network. Insufficient levels of iodide can lead to increased expression or activity of several pathways, including vascular endothelial growth factor (VEGF). The VEGF protein fuel vessel growth (angiogenesis) and therefore enhances the nutrients available to surrounding cells. Alternatively, normal/surplus iodide levels can have inhibitory effects on angiogenesis. Varying levels of iodide in the thyroid can influence thyroid carcinoma cell proliferation and angiogenesis via regulation of the hypoxia inducible factor-1 (HIF-1) and VEGF-dependent pathway. We have reviewed a number of studies to investigate how the effect of iodide on angiogenic and oxidative stress regulation can affect the viability of thyroid carcinoma cells. The various studies outlined give key insights to the role of iodide in thyroid follicles function and vascular growth, generally highlighting that insufficient levels of iodide stimulate pathways resulting in vascular growth, andviceversanormal/surplus iodide levels inhibit such pathways. Intriguingly, TSH and iodine levels differentially regulate the expression levels of angiogenic factors. All cells, including carcinoma cells, increase uptake of blood nutrients, meaning the vascular profile is influential to tumor growth and progression. Importantly, variation in the iodine concentrations also influence BRAFV600E-mediated oncogenic activity and might deregulate tumor proliferation. Although the mechanisms are not well eluted, iodine concentrations and metabolism might have a crucial influence on thyroid carcinoma cell viability via regulation of different molecular pathways, including angiogenesis regulatory autocrine and microenvironment-mediated signals.
authors.affiliation: Laboratory of human thyroid cancers preclinical and translational research, Division of Experimental Pathology, Cancer Research Institute (CRI), Cancer Center, Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.|Department of Pathology, Center for Vascular Biology Research (CVBR), Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
authors.forename: Kayla
authors.initials: K
authors.lastname: Daniell
authors.affiliation: Laboratory of human thyroid cancers preclinical and translational research, Division of Experimental Pathology, Cancer Research Institute (CRI), Cancer Center, Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.|Department of Pathology, Center for Vascular Biology Research (CVBR), Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
authors.forename: Carmelo
authors.initials: C
authors.lastname: Nucera
mesh_terms: D002277:Carcinoma / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007455:Iodine / Q000378:metabolism*; D018977:Micronutrients / Q000378:metabolism*; D009389:Neovascularization, Pathologic / Q000378:metabolism* / Q000473:pathology; D018384:Oxidative Stress / Q000502:physiology; D013964:Thyroid Neoplasms / Q000378:metabolism* / Q000473:pathology; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D018977:Micronutrients; D042461:Vascular Endothelial Growth Factor A; D007455:Iodine
keywords: BRAFV600E; HIF-1; TGFB; VEGF; angiogenesis; iodine; pre-clinical model; thyroid cancer; tumor growth