Cholesterol and 27-hydroxycholesterol promote thyroid carcinoma aggressiveness
Por:
Revilla, G, Pons, MD, Baila-Rueda, L, Garcia-Leon, A, Santos, D, Cenarro, A, Magalhaes, M, Blanco, RM, Mora, A, Perez, JI, Sabe, G, Gonzalez, C, Fuste, V, Lerma, E, Faria, MD, de Leiva, A, Corcoy, R, Escola-Gil, JC, Mato, E
Publicada:
16 jul 2019
Resumen:
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.
Filiaciones:
Revilla, G:
Hosp Santa Creu & Sant Pau, IIB St Pau, Barcelona, Spain
Univ Autonoma Barcelona, Dept Bioquim Biol Mol & Biomed, Barcelona, Spain
Pons, MD:
Hosp Santa Creu & Sant Pau, Dept Endocrinol EDUAB HSP, Barcelona, Spain
Hosp Santa Creu & Sant Pau, IIB St Pau, Barcelona, Spain
Baila-Rueda, L:
Hosp Univ Miguel Servet, IIS Aragon, Unidad Clin & Invest Lipidos & Arteriosclerosis, Zaragoza, Spain
CIBERCV, CIBER Enfermedades Cardiovasc, Madrid, Spain
Garcia-Leon, A:
Hosp Santa Creu & Sant Pau, IIB St Pau, Barcelona, Spain
Santos, D:
Hosp Santa Creu & Sant Pau, IIB St Pau, Barcelona, Spain
CIBERDEM, Madrid, Spain
Cenarro, A:
CIBERCV, CIBER Enfermedades Cardiovasc, Madrid, Spain
Magalhaes, M:
Hosp Fed Univ Maranhao HUUFMA, Serv Endocrinol, Clin Res Ctr CEPEC, Sao Luis, Maranhao, Brazil
Blanco, RM:
CIBER BBN, Madrid, Spain
Mora, A:
Hosp Santa Creu & Sant Pau, IIB St Pau, Barcelona, Spain
Hosp Santa Creu & Sant Pau, Dept Gen Surg, Barcelona, Spain
Autonomous Univ Barcelona UAB, Med Dept, Barcelona, Spain
Perez, JI:
Hosp Santa Creu & Sant Pau, Dept Gen Surg, Barcelona, Spain
Sabe, G:
Hosp Santa Creu & Sant Pau, IIB St Pau, Barcelona, Spain
Gonzalez, C:
Hosp Santa Creu & Sant Pau, Dept Endocrinol EDUAB HSP, Barcelona, Spain
CIBER BBN, Madrid, Spain
Fuste, V:
Hosp Santa Creu & Sant Pau, IIB St Pau, Barcelona, Spain
UAB, Hosp Santa Creu & St Pau, Dept Anat Pathol, Barcelona, Spain
Lerma, E:
Hosp Santa Creu & Sant Pau, IIB St Pau, Barcelona, Spain
UAB, Hosp Santa Creu & St Pau, Dept Anat Pathol, Barcelona, Spain
Faria, MD:
Hosp Fed Univ Maranhao HUUFMA, Serv Endocrinol, Clin Res Ctr CEPEC, Sao Luis, Maranhao, Brazil
de Leiva, A:
Hosp Santa Creu & Sant Pau, IIB St Pau, Barcelona, Spain
CIBER BBN, Madrid, Spain
Corcoy, R:
Hosp Santa Creu & Sant Pau, Dept Endocrinol EDUAB HSP, Barcelona, Spain
CIBER BBN, Madrid, Spain
Autonomous Univ Barcelona UAB, Med Dept, Barcelona, Spain
Escola-Gil, JC:
Hosp Santa Creu & Sant Pau, IIB St Pau, Barcelona, Spain
Univ Autonoma Barcelona, Dept Bioquim Biol Mol & Biomed, Barcelona, Spain
CIBERDEM, Madrid, Spain
Mato, E:
Hosp Santa Creu & Sant Pau, Dept Endocrinol EDUAB HSP, Barcelona, Spain
CIBER BBN, Madrid, Spain
Gold, Green Published
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