Abstract
The development of prognostic indicators of breast cancer metastatic risk could reduce the number of patients receiving chemotherapy for tumors with low metastatic potential. Recent evidence points to a critical role for cell metabolism in driving breast cancer metastasis. Endogenous fluorescence intensity of nicotinamide adenine dinucleotide (NADH) and flavin adenine dinucleotide (FAD) can provide a label-free method for assessing cell metabolism. We report the optical redox ratio of FAD/(FAD + NADH) of four isogenic triple-negative breast cancer cell lines with varying metastatic potential. Under normoxic conditions, the redox ratio increases with increasing metastatic potential (168FARN>4T07>4T1), indicating a shift to more oxidative metabolism in cells capable of metastasis. Reoxygenation following acute hypoxia increased the redox ratio by 43 ± 9% and 33 ± 4% in the 4T1 and 4T07 cells, respectively; in contrast, the redox ratio decreased 14 ± 7% in the non-metastatic 67NR cell line. These results demonstrate that the optical redox ratio is sensitive to the metabolic adaptability of breast cancer cells with high metastatic potential and could potentially be used to measure dynamic functional changes that are indicative of invasive or metastatic potential.
Highlights
About 90% of breast cancer patients die due to metastatic spread and not due to the primary tumor
Adjuvant chemotherapy reduces the risk of metastatic recurrence by at least 30% [2], and can be of significant benefit in patients classified as high risk based on the previously described prognostic indicators
To evaluate the ability of the optical redox ratio to report on dynamic changes in oxygen consumption, we acquired images corresponding to the fluorescence emission channels of NADH and flavin adenine dinucleotide (FAD) (Fig. 1(A)) from 4T1 breast cancer cells at baseline and after sequential addition of 3 mitochondrial inhibitors/uncouplers, similar to the Seahorse metabolic flux assay
Summary
About 90% of breast cancer patients die due to metastatic spread and not due to the primary tumor. Adjuvant chemotherapy reduces the risk of metastatic recurrence by at least 30% [2], and can be of significant benefit in patients classified as high risk based on the previously described prognostic indicators. For early-stage breast cancers with good prognosis (
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