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The Influence of Adipocyte Secretome on Selected Metabolic Fingerprints of Breast Cancer Cell Lines Representing the Four Major Breast Cancer Subtypes.

Biochemistry Unit, Biomedicine Department, FMUP-Faculty of Medicine, University of Porto, 4200-450 Porto, Portugal. i3S-Instituto de Investigação e Inovação em Saúde, Universidade do Porto, 4200-135 Porto, Portugal. Clinical and Experimental Endocrinology, UMIB-Unit for Multidisciplinary Research in Biomedicine, ICBAS-School of Medicine and Biomedical Sciences, University of Porto, 4050-313 Porto, Portugal. ITR-Laboratory for Integrative and Translational Research in Population Health, University of Porto, 4099-002 Porto, Portugal. Laboratory of Physiology, Department of Imuno-Physiology & Pharmacology, ICBAS-School of Medicine and Biomedical Sciences, University of Porto, 4050-313 Porto, Portugal. LAQV-REQUIMTE, Department of Chemistry, University of Aveiro, 3810-193 Aveiro, Portugal. Department of Pathology, Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal. T-BIO-Center for Translational Health and Medical Biotechnology Research, 4200-072 Porto, Portugal. Department of Clinical Pathology, São João Hospital Centre, 4200-319 Porto, Portugal. FCS/HEFP/UFP-Faculty of Health Sciences, Fernando Pessoa University, Fernando Pessoa Teaching Hospital, 4249-004 Porto, Portugal.

Cells. 2023;(17)
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Abstract

Molecular subtype (MS) is one of the most used classifications of breast cancer (BC). Four MSs are widely accepted according to receptor expression of estrogen, progesterone, and HER2. The impact of adipose tissue on BC MS metabolic impairment is still unclear. The present work aims to elucidate the metabolic alterations in breast cancer cell lines representing different MSs subjected to adipocyte associated factors. Preadipocytes isolated from human subcutaneous adipose tissue were differentiated into mature adipocytes. MS representative cell lines were exposed to mature adipocyte secretome. Extracellular medium was collected for metabolomics and RNA was extracted to evaluate enzymatic expression by RT-PCR. Adipocyte secretome exposure resulted in a decrease in the Warburg effect rate and an increase in cholesterol release. HER2+ cell lines (BT-474 and SK-BR-3) exhibited a similar metabolic pattern, in contrast to luminal A (MCF-7) and triple negative (TN) (MDA-MB-231), both presenting identical metabolisms. Anaplerosis was found in luminal A and TN representative cells, whereas cataplerotic reactions were likely to occur in HER2+ cell lines. Our results indicate that adipocyte secretome affects the central metabolism distinctly in each BC MS representative cell line.