Cholesterol and 27-hydroxycholesterol promote thyroid carcinoma aggressiveness

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...

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Detalles Bibliográficos
Autores: Revilla, Giovanna|||0000-0003-2971-5651, Pons, Monica de Pablo, Baila-Rueda, Lucía, Garcia León, Annabel|||0000-0003-3007-9306, Santos, David|||0000-0003-1157-4969, Cenarro, Ana, Magalhaes, Marcelo, Blanco, R. M., Moral, Antonio|||0000-0001-5551-0145, Pérez, José Ignacio, Sabé, Gerard, González, Cintia|||0000-0003-2551-9979, Fuste, Victoria|||0000-0001-5065-3737, Lerma Puertas, Enrique|||0000-0001-7908-2747, Faria, Manuel dos Santos, De Leiva Hidalgo, Alberto|||0000-0002-0419-6771, Corcoy i Pla, Rosa|||0000-0001-5055-6814, Escolà-Gil, Joan Carles|||0000-0001-9021-2485, Mato, Eugènia|||0000-0001-8121-9335
Tipo de recurso: artículo
Fecha de publicación:2019
País:España
Institución:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:223318
Acceso en línea:https://ddd.uab.cat/record/223318
https://dx.doi.org/urn:doi:10.1038/s41598-019-46727-2
Access Level:acceso abierto
Palabra clave:Lipoproteins
Thyroid cancer
Descripción
Sumario: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.

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