AUTHOR=Fung Anthony A. , Hoang Khang , Zha Honghao , Chen Derek , Zhang Wenxu , Shi Lingyan 

TITLE=Imaging Sub-Cellular Methionine and Insulin Interplay in Triple Negative Breast Cancer Lipid Droplet Metabolism

JOURNAL=Frontiers in Oncology

VOLUME=12

YEAR=2022

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2022.858017

DOI=10.3389/fonc.2022.858017

ISSN=2234-943X

ABSTRACT=<p>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 (D<sub>2</sub>O) probed Raman scattering with label-free two-photon fluorescence (TPF) microscopy, we observed altered <italic>de novo</italic> 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.</p>