Author, as appears in the article.: Altuna-Coy A; Ruiz-Plazas X; Sánchez-Martin S; Ascaso-Til H; Prados-Saavedra M; Alves-Santiago M; Bernal-Escoté X; Segarra-Tomás J; R Chacón M
Department: Medicina i Cirurgia Ciències Mèdiques Bàsiques
URV's Author/s: Altuna Coy, Antonio / Alves Santiago, Marta / Ascaso Til, Helena / Bernal Escoté, Xana / Prados Saavedra, Manuel / Ruiz Plazas, Xavier / Sanchez Martin, Silvia / Segarra Tomas, Josep
Keywords: Prostate-cancer aggressiveness Prostate cancer Periprostatic adipose tissue Lipidomic Lipid metabolism De novo fatty acid synthesis prostate cancer lipidomic lipid metabolism gamma de novo fatty acid synthesis adipocytes
Abstract: Periprostatic adipose tissue (PPAT) plays a role in prostate cancer (PCa) progression. PPAT lipidomic composition study may allow us to understand the tumor metabolic microenvironment and provide new stratification factors.We used ultra-high-performance liquid chromatography-mass spectrometry-based non-targeted lipidomics to profile lipids in the PPAT of 40 patients with PCa (n = 20 with low-risk and n = 20 high-risk). Partial least squares-discriminant analysis (PLS-DA) and variable importance in projection (VIP) analysis were used to identify the most relevant features of PPAT between low- and high-risk PCa, and metabolite set enrichment analysis was used to detect disrupted metabolic pathways. Metabolic crosstalk between PPAT and PCa cell lines (PC-3 and LNCaP) was studied using ex vivo experiments. Lipid uptake and lipid accumulation were measured. Lipid metabolic-related genes (SREBP1, FASN, ACACA, LIPE, PPARG, CD36, PNPLA2, FABP4, CPT1A, FATP5, ADIPOQ), inflammatory markers (IL-6, IL-1B, TNFα), and tumor-related markers (ESRRA, MMP-9, TWIST1) were measured by RT-qPCR.Significant differences in the content of 67 lipid species were identified in PPAT samples between high- and low-risk PCa. PLS-DA and VIP analyses revealed a discriminating lipidomic panel between low- and high-risk PCa, suggesting the occurrence of disordered lipid metabolism in patients related to PCa aggressiveness. Functional analysis revealed that alterations in fatty acid biosynthesis, linoleic acid metabolism, and β-oxidation of very long-chain fatty acids had the greatest impact in the PPAT lipidome. Gene analyses of PPAT samples demonstrated that the expression of genes associated with de novo fatty acid synthesis such as FASN and ACACA were significantly lower in PPAT from high-risk PCa than in low-risk counterparts. This was accompanied by the overexpression of inflammatory markers (IL-6, IL-1B, and TNFα). Co-culture of PPAT explants with PCa cell lines revealed a reduced gene expression of lipid metabolic-related genes (CD36, FASN, PPARG, and CPT1A), contrary to that observed in co-cultured PCa cell lines. This was followed by an increase in lipid uptake and lipid accumulation in PCa cells. Tumor-related genes were increased in co-cultured PCa cell lines.Disturbances in PPAT lipid metabolism of patients with high-risk PCa are associated with tumor cell metabolic changes.© 2022. The Author(s).
Thematic Areas: Saúde coletiva Medicine, general & internal Medicine (miscellaneous) Medicine (all) Medicina veterinaria Medicina ii Medicina i General medicine Ciências biológicas iii Ciências biológicas ii Ciências biológicas i
licence for use: https://creativecommons.org/licenses/by/3.0/es/
Author's mail: xana.bernal@urv.cat xavier.ruiz@urv.cat manuel.prados@urv.cat helena.ascaso@urv.cat josep.segarra@urv.cat silvia.sanchezm@estudiants.urv.cat antonio.altuna@estudiants.urv.cat marta.alves@estudiants.urv.cat
Record's date: 2024-09-07
Papper version: info:eu-repo/semantics/publishedVersion
Link to the original source: https://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-022-02457-3
Licence document URL: https://repositori.urv.cat/ca/proteccio-de-dades/
Papper original source: Bmc Medicine. 20 (1): 255-255
APA: Altuna-Coy A; Ruiz-Plazas X; Sánchez-Martin S; Ascaso-Til H; Prados-Saavedra M; Alves-Santiago M; Bernal-Escoté X; Segarra-Tomás J; R Chacón M (2022). The lipidomic profile of the tumoral periprostatic adipose tissue reveals alterations in tumor cell's metabolic crosstalk. Bmc Medicine, 20(1), 255-255. DOI: 10.1186/s12916-022-02457-3
Article's DOI: 10.1186/s12916-022-02457-3
Entity: Universitat Rovira i Virgili
Journal publication year: 2022
Publication Type: Journal Publications
Repositori URV