Cholesterol and 27-hydroxycholesterol promote thyroid carcinoma aggressiveness

• Published in: Scientific reports Vol. 9; no. 1; pp. 10260 - 13
• Main Authors: Revilla, Giovanna, Pons, Monica de Pablo, Baila-Rueda, Lucía, García-León, Annabel, Santos, David, Cenarro, Ana, Magalhaes, Marcelo, Blanco, R M, Moral, Antonio, Ignacio Pérez, José, Sabé, Gerard, González, Cintia, Fuste, Victoria, Lerma, Enrique, Faria, Manuel Dos Santos, de Leiva, Alberto, Corcoy, Rosa, Carles Escolà-Gil, Joan, Mato, Eugenia
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 16.07.2019; Nature Publishing Group UK
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; Apolipoprotein B; Biomarkers, Tumor - blood; Breast; Breast cancer; Carcinoma, Papillary - genetics; Carcinoma, Papillary - metabolism; Carcinoma, Papillary - pathology; Cell Line, Tumor; Cell migration; Cell Movement; Cell Proliferation; Cholestanetriol 26-Monooxygenase - genetics; Cholesterol; Cholesterol, LDL - blood; Cytochrome P450 Family 7 - genetics; Endometrial cancer; Endometrium; Female; Gene expression; Gene Expression Regulation, Neoplastic; Humans; Hydroxycholesterols - metabolism; Hydroxylase; Hydroxymethylglutaryl CoA Reductases - genetics; Lipid metabolism; Low density lipoprotein; Male; MAP Kinase Signaling System; Metabolism; Metabolites; Metastases; Middle Aged; Papillary thyroid carcinoma; Phosphatidylinositol 3-Kinases - metabolism; Receptors, LDL - genetics; Reductase; Steroid Hydroxylases - genetics; Thyroid; Thyroid cancer; Thyroid Carcinoma, Anaplastic - genetics; Thyroid Carcinoma, Anaplastic - metabolism; Thyroid Carcinoma, Anaplastic - pathology; Thyroid Neoplasms - genetics; Thyroid Neoplasms - metabolism; Thyroid Neoplasms - pathology; TOR Serine-Threonine Kinases - metabolism; Tumors; Young Adult
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-019-46727-2

Cholesterol mediates its proliferative and metastatic effects via the metabolite 27-hydroxycholesterol (27-HC), at least in breast and endometrial cancer. We determined the serum lipoprotein profile, intratumoral cholesterol and 27-HC levels in a cohort of patients with well-differentiated papillary thyroid carcinoma (PTC; low/intermediate and high risk), advanced thyroid cancers (poorly differentiated, PDTC and anaplastic thyroid carcinoma, ATC) and benign thyroid tumors, as well as the expression of genes involved in cholesterol metabolism. We investigated the gene expression profile, cellular proliferation, and migration in Nthy-ori 3.1 and CAL-62 cell lines loaded with human low-density lipoprotein (LDL). Patients with more aggressive tumors (high-risk PTC and PDTC/ATC) showed a decrease in blood LDL cholesterol and apolipoprotein B. These changes were associated with an increase in the expression of the thyroid's LDL receptor, whereas 3-hydroxy-3-methylglutaryl-CoA reductase and 25-hydroxycholesterol 7-alpha-hydroxylase were downregulated, with an intratumoral increase of the 27-HC metabolite. Furthermore, LDL promoted proliferation in both the Nthy-ori 3.1 and CAL-62 thyroid cellular models, but only in ATC cells was its cellular migration increased significantly. We conclude that cholesterol and intratumoral accumulation of 27-HC promote the aggressive behavior process of PTC. Targeting cholesterol metabolism could be a new therapeutic strategy in thyroid tumors with poor prognosis.