Optical redox ratio differentiates breast cancer cell lines based on estrogen receptor status

Julie Hanson Ostrander, Christine M. McMahon, Siya Lem, Stacy R. Millon, J. Quincy Brown, Victoria L. Seewaldt, Nimmi Ramanujam

Research output: Contribution to journalArticle

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Abstract

Autofluorescence spectroscopy is a powerful imaging technique that exploits endogenous fluorophores. The endogenous fluorophores NADH and flavin adenine dinucleotide (FAD) are two of the principal electron donors and acceptors in cellular metabolism, respectively. The optical oxidation-reduction (redox) ratio is a measure of cellular metabolism and can be determined by the ratio of NADH/FAD. We hypothesized that there would be a significant difference in the optical redox ratio of normal mammary epithelial cells compared with breast tumor cell lines and that estrogen receptor (ER)-positive cells would have a higher redox ratio than ER-negative cells. To test our hypothesis, the optical redox ratio was determined by collecting the fluorescence emission for NADH and FAD via confocal microscopy. We observed a statistically significant increase in the optical redox ratio of cancer compared with normal cell lines (P < 0.05). Additionally, we observed a statistically significant increase in the optical redox ratio of ER(+) breast cancer cell lines. The level of ESR1 expression, determined by real-time PCR, directly correlated with the optical redox ratio (Pearson's correlation coefficient = 0.8122, P = 0.0024). Furthermore, treatment with tamoxifen and ICI 182,870 statistically decreased the optical redox ratio of only ER(+) breast cancer cell lines. The results of this study raise the important possibility that fluorescence spectroscopy can be used to identify subtypes of breast cancer based on receptor status, monitor response to therapy, or potentially predict response to therapy. This source of optical contrast could be a potentially useful tool for drug screening in preclinical models.

Original languageEnglish (US)
Pages (from-to)4759-4766
Number of pages8
JournalCancer Research
Volume70
Issue number11
DOIs
StatePublished - Jun 1 2010

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Estrogen Receptors
Oxidation-Reduction
Breast Neoplasms
Cell Line
Flavin-Adenine Dinucleotide
NAD
Preclinical Drug Evaluations
Fluorescence Spectrometry
Tamoxifen
Tumor Cell Line
Confocal Microscopy
Real-Time Polymerase Chain Reaction
Spectrum Analysis
Breast
Fluorescence
Epithelial Cells
Electrons
Therapeutics

Cite this

Ostrander, J. H., McMahon, C. M., Lem, S., Millon, S. R., Brown, J. Q., Seewaldt, V. L., & Ramanujam, N. (2010). Optical redox ratio differentiates breast cancer cell lines based on estrogen receptor status. Cancer Research, 70(11), 4759-4766. https://doi.org/10.1158/0008-5472.CAN-09-2572

Optical redox ratio differentiates breast cancer cell lines based on estrogen receptor status. / Ostrander, Julie Hanson; McMahon, Christine M.; Lem, Siya; Millon, Stacy R.; Brown, J. Quincy; Seewaldt, Victoria L.; Ramanujam, Nimmi.

In: Cancer Research, Vol. 70, No. 11, 01.06.2010, p. 4759-4766.

Research output: Contribution to journalArticle

Ostrander, JH, McMahon, CM, Lem, S, Millon, SR, Brown, JQ, Seewaldt, VL & Ramanujam, N 2010, 'Optical redox ratio differentiates breast cancer cell lines based on estrogen receptor status', Cancer Research, vol. 70, no. 11, pp. 4759-4766. https://doi.org/10.1158/0008-5472.CAN-09-2572
Ostrander, Julie Hanson ; McMahon, Christine M. ; Lem, Siya ; Millon, Stacy R. ; Brown, J. Quincy ; Seewaldt, Victoria L. ; Ramanujam, Nimmi. / Optical redox ratio differentiates breast cancer cell lines based on estrogen receptor status. In: Cancer Research. 2010 ; Vol. 70, No. 11. pp. 4759-4766.
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