Abstract
Triple-negative breast cancer (TNBC) is a highly diverse group of cancers with limited treatment options, responsible for about 15% of all breast cancers. TNBC cells differ from each other in many ways such as gene expression, metabolic activity, tumorigenicity, and invasiveness. Recently, many research and clinical efforts have focused on metabolically targeted therapy for TNBC. Metabolic characterization of TNBC cell lines can facilitate the assessment of therapeutic effects and assist in metabolic drug development. Herein, we used optical redox imaging (ORI) techniques to characterize TNBC subtypes metabolically. We found that various TNBC cell lines had differing redox statuses (levels of reduced nicotinamide adenine dinucleotide (NADH), oxidized flavin adenine dinucleotide (FAD), and the redox ratio (FAD/(NADH+FAD)). We then metabolically perturbed the cells with mitochondrial inhibitors and an uncoupler and performed ORI accordingly. As expected, we observed that these TNBC cell lines had similar response patterns to the metabolic perturbations. However, they exhibited differing redox plasticity. These results suggest that subtypes of TNBC cells are different metabolically and that ORI can serve as a sensitive technique for the metabolic profiling of TNBC cells.
Highlights
Triple-negative breast cancer (TNBC) is characterized by the lack of expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) [1]
Xu (*) Britton Chance Laboratory of Redox Imaging, Department of Radiology and Johnson Research Foundation, Department of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA e-mail: hexu2@pennmedicine.upenn.edu observed that these TNBC cell lines had similar response patterns to the metabolic perturbations. They exhibited differing redox plasticity. These results suggest that subtypes of TNBC cells are different metabolically and that optical redox imaging (ORI) can serve as a sensitive technique for the metabolic profiling of TNBC cells
We report the use of ORI as a tool in differentiating the mitochondrial redox status among four TNBC cell lines (MDA-MB-231 and MDA-MB-436 mesenchymal-like, MDA-MB468 basal-like 1, HCC1806 basal-like 2) and characterizing their redox plasticity under metabolic modulations
Summary
Triple-negative breast cancer (TNBC) is characterized by the lack of expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) [1]. We report the use of ORI as a tool in differentiating the mitochondrial redox status among four TNBC cell lines (MDA-MB-231 and MDA-MB-436 mesenchymal-like, MDA-MB468 basal-like 1, HCC1806 basal-like 2) and characterizing their redox plasticity under metabolic modulations. Such characterizations could provide useful information for the metabolic stratification of TNBC cell lines
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