The diverse metabolic heterogeneity of stem cells in a BRCA+/-breast cancer population.

Abstract

Breast cancers are very heterogeneous tissues constituted by epithelial cancer cells and an abnormal tumor microenvironment – cancer-associated fibroblasts (CAFs), activated adipocytes, mesenchymal stem cells (MSCs), and others. The aim of the study is to cancer cells and their microenvironment, which behave like a complex and heterogeneous metabolic ecosystem, where cancer cells can reprogram their metabolism as a result of interaction with the components of the microenvironment. The study was based on cancer stem cells (CSC) that were isolated from breast tumors by magnetic separation (AutoMACS). We used spectrophotometric methods for the measurement of aldehyde dehydrogenase (ALDH) enzymatic activity. For these experiments, we used breast cancer and normal stem cell lines. Analyses showed that the proportion of BRCA+ CSC cells was in accordance with the relatively low percentages of CSCs in BRCA+ tumors. ALHD was significantly higher in the CSCs-high BRCA+ breast cancer and CSCs-low BRCA- breast cancer cells, compared with the CSCs-low BRCA+ breast cancer. Breast cancer from BRCA mutation carriers harbor more “high-energy” cell sub-populations than “low-energy” and have their more aggressive phenotype. Key oncogenic pathways known to be dysregulated in breast cancer also regulate stem-cell behavior.