Fung Anthony A, Hoang Khang, Zha Honghao, Chen Derek, Zhang Wenxu, Shi Lingyan
Department of Bioengineering, University of California San Diego, La Jolla, CA, United States.
Front Oncol. 2022 Mar 10;12:858017. doi: 10.3389/fonc.2022.858017. eCollection 2022.
Triple negative breast cancer (TNBC) is a particularly aggressive cancer subtype that is difficult to diagnose due to its discriminating epidemiology and obscure metabolome. For the first time, 3D spatial and chemometric analyses uncover the unique lipid metabolome of TNBC under the tandem modulation of two key metabolites - insulin and methionine - using non-invasive optical techniques. By conjugating heavy water (DO) probed Raman scattering with label-free two-photon fluorescence (TPF) microscopy, we observed altered lipogenesis, 3D lipid droplet morphology, and lipid peroxidation under various methionine and insulin concentrations. Quantitative interrogation of both spatial and chemometric lipid metabolism under tandem metabolite modulation confirms significant interaction of insulin and methionine, which may prove to be critical therapeutic targets, and proposes a powerful optical imaging platform with subcellular resolution for metabolic and cancer research.
三阴性乳腺癌（TNBC）是一种侵袭性特别强的癌症亚型，因其独特的流行病学特征和模糊的代谢组而难以诊断。研究首次运用非侵入性光学技术，通过三维空间和化学计量学分析，揭示了在两种关键代谢物——胰岛素和蛋氨酸的串联调节下TNBC独特的脂质代谢组。通过将重水（D₂O）探测的拉曼散射与无标记双光子荧光（TPF）显微镜相结合，我们观察到在不同蛋氨酸和胰岛素浓度下，脂肪生成、三维脂滴形态以及脂质过氧化均发生了改变。对串联代谢物调节下的空间和化学计量脂质代谢进行定量分析，证实了胰岛素和蛋氨酸之间存在显著相互作用，这可能是关键的治疗靶点，并提出了一个具有亚细胞分辨率的强大光学成像平台，用于代谢和癌症研究。
