Revilla, Giovanna2; Mato, Eugenia1; Garcia-León, Annabel3; Escolà, Joan Carles3; Blancol, Rosa Mª1; Santos, David3; González, Cintia2,1; Moral, Antonio4; Pérez, José Ignacio4; Blanco-Vaca, Francisco3; de Leiva, Alberto2,1
1 Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN),
2 Department of Endocrinology-EDUAB-HSP, Hospital de Sant Pau, Autonomous University, Barcelona
3 IIB-SantPau, CIBERDEM (Diabetes and Associated Metabolic Diseases),
4 General Surgery, Hospital de Sant Pau, Autonomous University, Barcelona, Spain
Background/ Purpose: LDL and HDL are important lipoproteins involved in cell growth in some solid tumors. However, the relationship between cholesterol metabolic alterations in the epithelial thyroid neoplasm (ETN) remains unknown. We aimed to investigate the lipid profile and the role of specific genes involved in the cholesterol metabolism in human ETN and thyroid cell lines.
Methods: Serum lipoprotein profile of patients with 14 adenomas, well-differentiated and poorly-differentiated thyroid cancer (28 WDTC, 8 PDTC), were analyzed. Furthermore, Nthy-ori (normal thyroid), Cal-62 (anaplastic), TPC-1 (papillary) were treated with LDL (100µM of apoB) and HDL (100µM of apoA-I). In both tissue and cell samples we determined by qRT-PCR the gene expression of: ATP-binding cassette (ABCA1), apolipoprotein A1 (ABCG1), LDL receptor (LDLR), Scavenger receptor type B-I (SCARB1), Esterol 27-hidroxilasa (CYP27A1), Oxysterol 7?-Hidroxilasa (CYP7B1), 3-Hidroxi-3-Metilglutaril-CoA reductase (HMGCR). Proliferation study was measured by MTT assay. Statistical analyses were performed by GraphPad Prism and DataAssist softwares.
Results: PDTC had lower mean serum apo B levels (0.66 ± 0.02 g/L) than adenomas (0.85 ± 0.04 g/L) and WDTC (0.89 ± 0.04 g/L). No significant changes were found for other lipoproteins. A significant down-regulation of HMGCR, CYP7B1, CYP27A1 and ApoA1 gene expression was detected for PDTC. Cells treated with LDL promoted cell proliferation, migration and down-regulation of LDLR, CYP27A1 and HMGCR gene expression. In contrast, HDL treatment did not affect cellular proliferation but depicted down-regulation of ABCA1 and ABCG1 gene expression.
Conclusion: These findings indicate a possible intervention of cholesterol metabolism in ETN with aggressive behavior.