1. Tissue cholesterol metabolism and prostate cancer aggressiveness: Ethno-geographic variations.
- Author
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Lethongsavarn V, Pinault M, Diedhiou A, Guimaraes C, Guibon R, Bruyère F, Mathieu R, Rioux-Leclercq N, Multigner L, Brureau L, Fournier G, Doucet L, Blanchet P, and Fromont G
- Subjects
- ATP Binding Cassette Transporter 1 analysis, Black People statistics & numerical data, Epithelial-Mesenchymal Transition, France epidemiology, Humans, Immunohistochemistry, Lipid Metabolism, Male, Middle Aged, Sterol Regulatory Element Binding Protein 2 analysis, White People statistics & numerical data, Adipose Tissue metabolism, Adipose Tissue pathology, Cholesterol metabolism, Prostate pathology, Prostatic Neoplasms ethnology, Prostatic Neoplasms metabolism, Prostatic Neoplasms pathology, Zinc Finger E-box-Binding Homeobox 1 analysis
- Abstract
Background: Prostate cancer (PCa) is more frequent and more aggressive in populations of African descent than in Caucasians. Since the fatty acid composition of peri-prostatic adipose tissue (PPAT) has been shown to differ according to the ethno-geographic origin and is involved in PCa aggressiveness, we aimed to analyze the cholesterol content of PPAT from Caucasian and African-Caribbean patients, in correlation with markers of disease aggressiveness and cholesterol metabolism in cancer tissues., Methods: The quantification of cholesterol in PPAT was analyzed in 52 Caucasian and 52 African-Caribbean PCa patients, with in each group 26 indolent tumors (ISUP Group1 and pT2) and 26 potentially aggressive tumors (ISUP Group 3-5 and/or pT3). The expression of proteins involved in cholesterol metabolism was analyzed by immunohistochemistry on cancer tissue samples included in tissue microarrays., Results: The amount of cholesterol esters was lower in PPAT from African-Caribbean patients compared with Caucasians, without any correlation with markers of disease aggressiveness. In cancer tissues from African-Caribbean patients, the expression of ABCA1 (involved in cholesterol efflux) was decreased, and that of SREBP-2 (involved in cholesterol uptake) was increased. In both groups of patients, SREBP-2 expression was strongly associated with that of Zeb1, a key player in the epithelial-to-mesenchymal transition (EMT) process., Conclusion: These results suggest that cholesterol metabolism differs according to the ethno-geographic origin, in both PPAT and cancer tissues. In African-Caribbeans, the orientation towards accumulation of cholesterol in cancer cells is associated with a more frequent state of EMT, which may promote PCa aggressiveness in this population., (© 2021 Wiley Periodicals LLC.)
- Published
- 2021
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