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Longitudinal FRET Imaging of Glucose and Lactate Dynamics and Response to Therapy in Breast Cancer Cells

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A Correction to this article was published on 02 November 2021

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Abstract

Purpose

The reprogramming of cellular metabolism is a hallmark of cancer. The ability to noninvasively assay glucose and lactate concentrations in cancer cells would improve our understanding of the dynamic changes in metabolic activity accompanying tumor initiation, progression, and response to therapy. Unfortunately, common approaches for measuring these nutrient levels are invasive or interrupt cell growth. This study transfected FRET reporters quantifying glucose and lactate concentration into breast cancer cell lines to study nutrient dynamics and response to therapy.

Procedures

Two FRET reporters, one assaying glucose concentration and one assaying lactate concentration, were stably transfected into the MDA-MB-231 breast cancer cell line. Correlation between FRET measurements and ligand concentration were measured using a confocal microscope and a cell imaging plate reader. Longitudinal changes in glucose and lactate concentration were measured in response to treatment with CoCl2, cytochalasin B, and phloretin which, respectively, induce hypoxia, block glucose uptake, and block glucose and lactate transport.

Results

The FRET ratio from the glucose and lactate reporters increased with increasing concentration of the corresponding ligand (p < 0.005 and p < 0.05, respectively). The FRET ratio from both reporters was found to decrease over time for high initial concentrations of the ligand (p < 0.01). Significant differences in the FRET ratio corresponding to metabolic inhibition were found when cells were treated with glucose/lactate transporter inhibitors.

Conclusions

FRET reporters can track intracellular glucose and lactate dynamics in cancer cells, providing insight into tumor metabolism and response to therapy over time.

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Funding

This project was supported by CPRIT for funding through RR160005 and RR160093, and the National Institutes of Health for funding through NCI U01CA174706, U01CA142565, and R01CA186193. T.E.Y is a CPRIT Scholar in Cancer Research. H.-C.Y. acknowledges the support from the Welch Foundation (F-1833), National Science Foundation (2029266) and National Institutes of Health (EY033106).

Author information

Authors and Affiliations

  1. Department of Biomedical Engineering, The University of Texas At Austin, Austin, TX, 78712, USA

    Jianchen Yang, Tessa Davis, Anum S. Kazerouni, Yuan-I. Chen, Meghan J. Bloom, Hsin-Chih Yeh & Thomas E. Yankeelov

  2. Texas Materials Institute, The University of Texas At Austin, Austin, TX, 78712, USA

    Hsin-Chih Yeh

  3. Department of Diagnostic Medicine, The University of Texas At Austin, 201 E. 24th Street, 1 University Station (C0200), Austin, TX, 78712, USA

    Thomas E. Yankeelov & John Virostko

  4. Department of Oncology, The University of Texas At Austin, Austin, TX, 78712, USA

    Thomas E. Yankeelov & John Virostko

  5. Oden Institute for Computational Engineering and Sciences, The University of Texas At Austin, Austin, TX, 78712, USA

    Thomas E. Yankeelov

  6. Livestrong Cancer Institutes, The University of Texas At Austin, Austin, TX, 78712, USA

    Thomas E. Yankeelov & John Virostko

  7. Department of Imaging Physics, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA

    Thomas E. Yankeelov

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  1. Jianchen Yang
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Contributions

JY, TEY, JV, and HY contributed to the study design, analysis, data interpretation, and manuscript draft. JY, TD, AKS, YC, and MJB contributed to data acquisition. All authors critically reviewed and approved the final version of the work.

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Correspondence to John Virostko.

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Yang, J., Davis, T., Kazerouni, A.S. et al. Longitudinal FRET Imaging of Glucose and Lactate Dynamics and Response to Therapy in Breast Cancer Cells. Mol Imaging Biol 24, 144–155 (2022). https://doi.org/10.1007/s11307-021-01639-4

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  • DOI: https://doi.org/10.1007/s11307-021-01639-4

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