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Updated: May 25, 2026
Autofluorescence Imaging to Evaluate Cellular Metabolism
Published on: November 15, 2021
Optical imaging of metabolism in HER2 overexpressing breast cancer cells
Alex Walsh1, Rebecca S Cook, Brent Rexer
1Department of Biomedical Engineering, Vanderbilt University, Station B, Box 1631, Nashville, Tennessee 37235, USA.
Abstract:
The optical redox ratio (fluorescence intensity of NADH divided by that of FAD), was acquired for a panel of breast cancer cell lines to investigate how overexpression of human epidermal growth factor receptor 2 (HER2) affects tumor cell metabolism, and how tumor metabolism may be altered in response to clinically used HER2-targeted therapies. Confocal fluorescence microscopy was used to acquire NADH and FAD auto-fluorescent images. The optical redox ratio was highest in cells overexpressing HER2 and lowest in triple negative breast cancer (TNBC) cells, which lack HER2, progesterone receptor, and estrogen receptor (ER). The redox ratio in ER-positive/HER2-negative cells was higher than what was seen in TNBC cells, but lower than that in HER2 overexpressing cells. Importantly, inhibition of HER2 using trastuzumab significantly reduced the redox ratio in HER2 overexpressing cells. Furthermore, the combinatorial inhibition of HER2 and ER decreased the redox ratio in ER+/HER2+ breast cancer cells to a greater extent than inhibition of either receptor alone. Interestingly, trastuzumab had little impact upon the redox ratio in a cell line selected for acquired resistance to trastuzumab. Taken together, these data indicate that the optical redox ratio measures changes in tumor metabolism that reflect the oncogenic effects of HER2 activity within the cell, as well as the response of the cell to therapeutic inhibition of HER2. Therefore, optical redox imaging holds the promise of measuring response and resistance to receptor-targeted breast cancer therapies in real time, which could potentially impact clinical decisions and improve patient outcome.
Insights
The optical redox ratio reveals how HER2 (human epidermal growth factor receptor 2) impacts breast cancer metabolism. This imaging technique can monitor treatment response and resistance to HER2-targeted therapies in real time.
Area of Science:
- Biochemistry
- Oncology
- Medical Imaging
Background:
- The optical redox ratio, derived from NADH and FAD fluorescence, reflects cellular metabolic state.
- Overexpression of human epidermal growth factor receptor 2 (HER2) is a key driver in certain breast cancers.
- Understanding metabolic alterations in response to HER2-targeted therapies is crucial for treatment optimization.
Purpose of the Study:
- To investigate the impact of HER2 overexpression on breast cancer cell metabolism using the optical redox ratio.
- To assess how tumor metabolism changes in response to HER2-targeted therapies.
- To evaluate the potential of optical redox imaging for real-time monitoring of treatment response and resistance.
Main Methods:
- Acquisition of optical redox ratios in a panel of breast cancer cell lines.
- Utilizing confocal fluorescence microscopy to capture NADH and FAD auto-fluorescent images.
- Employing targeted therapies like trastuzumab to inhibit HER2 and/or estrogen receptor (ER) signaling.
Main Results:
- The optical redox ratio was highest in HER2-overexpressing cells and lowest in triple-negative breast cancer (TNBC) cells.
- Trastuzumab significantly reduced the redox ratio in HER2-overexpressing cells.
- Combined HER2 and ER inhibition showed a greater metabolic impact than single-agent inhibition.
- Trastuzumab had minimal effect on cells resistant to the therapy, indicating altered metabolic adaptation.
Conclusions:
- The optical redox ratio serves as a sensitive indicator of metabolic changes driven by HER2 activity.
- Optical redox imaging can effectively measure cellular response and resistance to HER2-targeted breast cancer therapies.
- This imaging approach holds promise for real-time assessment of treatment efficacy, potentially guiding clinical decisions and improving patient outcomes.
