Alhallak Kinan, Rebello Lisa G, Muldoon Timothy J, Quinn Kyle P, Rajaram Narasimhan
Department of Biomedical Engineering, University of Arkansas, Fayetteville, AR 72701, USA.
Biomed Opt Express. 2016 Oct 3;7(11):4364-4374. doi: 10.1364/BOE.7.004364. eCollection 2016 Nov 1.
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.
乳腺癌转移风险预后指标的发展可以减少接受化疗的低转移潜能肿瘤患者的数量。最近的证据表明细胞代谢在驱动乳腺癌转移中起关键作用。烟酰胺腺嘌呤二核苷酸（NADH）和黄素腺嘌呤二核苷酸（FAD）的内源性荧光强度可以提供一种无标记的方法来评估细胞代谢。我们报告了四种具有不同转移潜能的同基因三阴性乳腺癌细胞系的FAD/（FAD + NADH）光学氧化还原比。在常氧条件下，氧化还原比随着转移潜能的增加而增加（168FARN>4T07>4T1），表明在具有转移能力的细胞中向更氧化的代谢转变。急性缺氧后的复氧分别使4T1和4T07细胞中的氧化还原比增加了43±9%和33±4%；相比之下，非转移性67NR细胞系中的氧化还原比下降了14±7%。这些结果表明，光学氧化还原比对具有高转移潜能的乳腺癌细胞的代谢适应性敏感，并有可能用于测量指示侵袭或转移潜能的动态功能变化。
