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Biomedical Optics Express

Biomedical Optics Express

  • Editor: Joseph A. Izatt
  • Vol. 3, Iss. 1 — Jan. 1, 2012
  • pp: 75–85

Optical imaging of metabolism in HER2 overexpressing breast cancer cells

Alex Walsh, Rebecca S. Cook, Brent Rexer, Carlos L. Arteaga, and Melissa C. Skala  »View Author Affiliations

Biomedical Optics Express, Vol. 3, Issue 1, pp. 75-85 (2012)

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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.

© 2011 OSA

OCIS Codes
(170.1530) Medical optics and biotechnology : Cell analysis
(170.1610) Medical optics and biotechnology : Clinical applications
(170.1790) Medical optics and biotechnology : Confocal microscopy
(170.2520) Medical optics and biotechnology : Fluorescence microscopy

ToC Category:
Cell Studies

Original Manuscript: October 13, 2011
Revised Manuscript: December 2, 2011
Manuscript Accepted: December 3, 2011
Published: December 9, 2011

Alex Walsh, Rebecca S. Cook, Brent Rexer, Carlos L. Arteaga, and Melissa C. Skala, "Optical imaging of metabolism in HER2 overexpressing breast cancer cells," Biomed. Opt. Express 3, 75-85 (2012)

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