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Updated: Nov 6, 2025
Studying Triple Negative Breast Cancer Using Orthotopic Breast Cancer Model
Published on: March 20, 2020
Optical Redox Imaging Differentiates Triple-Negative Breast Cancer Subtypes
Jinxia Jiang1, Min Feng1, Annemarie Jacob1
1Britton 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.
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.
Insights
Triple-negative breast cancer (TNBC) exhibits diverse metabolic profiles. Optical redox imaging (ORI) reveals distinct metabolic states and plasticity in TNBC subtypes, aiding targeted therapy development.
Area of Science:
- Biochemistry
- Oncology
- Medical Imaging
Background:
- Triple-negative breast cancer (TNBC) is an aggressive subtype with limited therapeutic options.
- TNBC heterogeneity extends to gene expression, metabolism, and invasiveness.
- Metabolically targeted therapies are a growing focus for TNBC treatment.
Purpose of the Study:
- To metabolically characterize diverse TNBC cell lines using optical redox imaging (ORI).
- To assess the metabolic plasticity of TNBC subtypes in response to perturbations.
- To establish ORI as a sensitive tool for TNBC metabolic profiling.
Main Methods:
- Utilized optical redox imaging (ORI) to measure cellular redox status, including NADH, FAD, and the FAD/(NADH+FAD) ratio.
- Metabolically perturbed TNBC cell lines using mitochondrial inhibitors and an uncoupler.
- Performed ORI before and after metabolic perturbations to evaluate cellular responses.
Main Results:
- Significant variations in baseline redox status (NADH, FAD, redox ratio) were observed across different TNBC cell lines.
- TNBC cell lines displayed similar response patterns to metabolic perturbations.
- Distinct differences in redox plasticity were identified among TNBC subtypes.
Conclusions:
- TNBC subtypes possess unique metabolic characteristics.
- ORI is a sensitive technique capable of differentiating metabolic profiles and plasticity in TNBC.
- Metabolic profiling via ORI can inform the development of targeted therapies for TNBC.
