Vitamin D in thyroid tumorigenesis and development

Abstract

Besides its classical role in bone and calcium homeostasis, 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), the active form of vitamin D, has many non-classical effects; antiproliferative, anti-apoptotic and prodifferentiating effects of 1,25(OH)2D3 have been described in several tumour types in preclinical models. This review focuses on the insights gained in the elucidation of the role of 1,25(OH)2D3 in the normal thyroid and in the pathogenesis, progression and treatment of thyroid cancer, the most common endocrine malignancy. An increasing amount of observations points towards a role for impaired 1,25(OH)2D3-VDR signalling in the occurrence and progression of thyroid cancer, and a potential for structural analogues in the multimodal treatment of dedifferentiated iodine-resistant thyroid cancer. A role for vitamin D in thyroid-related autoimmunity is less convincing and needs further study. Altered 1,25(OH)2D3-VDR signalling does not influence normal thyroid development nor thyrocyte function, but does affect C-cell function, at least in rodents. If these findings also apply to humans deserves further study.

Keywords: 1,25(OH)(2)D(3); 1α,25-dihydroxyvitamin D(3); 1α-hydroxylase; 24-hydroxylase; 25-OHD(3); 25-hydroxyvitamin D(3); ATC; CDK; CDKI; CEA; CT; CYP24A1; CYP27B1; DBP; DC; DIT; DTC; Duox; ER; FA; FGF23; FNAC; FTC; G-protein coupled receptor; GPCR; H&E; H(2)0(2); HAT; HDAC; HDACI; HPT; I-Tg; KO; MIT; MTC; NIS; PDS; PDTC; PMCA; PPI; PTC; PTH; RT-PCR; RXR; Rb; SAHA; T3; T4; TH; TKI; TPO; TRH; TSH; TSHR; Tg; US; VDR; VDRE; VEGF; WT; anaplastic thyroid cancer; calcitonin; carcinoembryogenic antigen; cyclin-dependent kinase; cyclin-dependent kinase inhibitor; dendritic cells; differentiated thyroid cancer; diiodotyrosine; dual oxidase; estrogen receptor; fibroblast growth factor-23; fine needle aspiration cytology; follicular adenoma; follicular thyroid cancer; haematoxylin and eosin; histone acetyltransferase; histone deacetylase; histone deacetylase inhibitor; hydrogen peroxide; hypothalamic-pituitary-thyroid; iodinated thyroglobulin; knockout; medullary thyroid cancer; monoiodotyrosine; papillary thyroid cancer; parathormone; pendrin; plasma membrane calcium ATPase; poorly differentiated thyroid cancer; proton pump inhibitor; retinoblastoma; retinoid X receptor; reverse transcriptase–polymerase chain reaction; sodium iodide symporter; suberoylanilide hydroxamic acid; thyroglobulin; thyroid hormone; thyroid peroxidase; thyroid stimulating hormone; thyroid stimulating hormone receptor; thyrotropin releasing hormone; thyroxine; tri-iodothyronine; tyrosine kinase inhibitor; ultrasound; vascular endothelial growth factor; vitamin D binding protein; vitamin D receptor; vitamin D responsive element; wild type..