Multimodal Metabolic Imaging Reveals Pigment Reduction and Lipid Accumulation in Metastatic Melanoma
Open Access
- 1 January 2021
- journal article
- research article
- Published by American Association for the Advancement of Science (AAAS) in BME Frontiers
Abstract
Objective and Impact Statement. Molecular signatures are needed for early diagnosis and improved treatment of metastatic melanoma. By high-resolution multimodal chemical imaging of human melanoma samples, we identify a metabolic reprogramming from pigmentation to lipid droplet (LD) accumulation in metastatic melanoma. Introduction. Metabolic plasticity promotes cancer survival and metastasis, which promises to serve as a prognostic marker and/or therapeutic target. However, identifying metabolic alterations has been challenged by difficulties in mapping localized metabolites with high spatial resolution. Methods. We developed a multimodal stimulated Raman scattering and pump-probe imaging platform. By time-domain measurement and phasor analysis, our platform allows simultaneous mapping of lipids and pigments at a subcellular level. Furthermore, we identify the sources of these metabolic signatures by tracking deuterium metabolites at a subcellular level. By validation with mass spectrometry, a specific fatty acid desaturase pathway was identified. Results. We identified metabolic reprogramming from a pigment-containing phenotype in low-grade melanoma to an LD-rich phenotype in metastatic melanoma. The LDs contain high levels of cholesteryl ester and unsaturated fatty acids. Elevated fatty acid uptake, but not de novo lipogenesis, contributes to the LD-rich phenotype. Monounsaturated sapienate, mediated by FADS2, is identified as an essential fatty acid that promotes cancer migration. Blocking such metabolic signatures effectively suppresses the migration capacity both in vitro and in vivo. Conclusion. By multimodal spectroscopic imaging and lipidomic analysis, the current study reveals lipid accumulation, mediated by fatty acid uptake, as a metabolic signature that can be harnessed for early diagnosis and improved treatment of metastatic melanoma.Funding Information
- National Institutes of Health (R35 GM136223, R33 CA223581, S10OD024993)
- Boston University
- IU Simon Cancer Center (P30 CA082709)
This publication has 67 references indexed in Scilit:
- Mutant p53 Disrupts Mammary Tissue Architecture via the Mevalonate PathwayCell, 2012
- Unsaturated Fatty Acids Drive Disintegrin and Metalloproteinase (ADAM)-dependent Cell Adhesion, Proliferation, and Migration by Modulating Membrane FluidityOnline Journal of Public Health Informatics, 2011
- Highly Sensitive Vibrational Imaging by Femtosecond Pulse Stimulated Raman LossThe Journal of Physical Chemistry Letters, 2011
- Pump-Probe Imaging Differentiates Melanoma from Melanocytic NeviScience Translational Medicine, 2011
- Acyl-coenzyme A:cholesterol acyltransferasesAmerican Journal of Physiology-Endocrinology and Metabolism, 2009
- In vivo characterization of melanin in melanocytic lesions: spectroscopic study on 1671 pigmented skin lesionsJournal of Biomedical Optics, 2009
- Label-Free Biomedical Imaging with High Sensitivity by Stimulated Raman Scattering MicroscopyScience, 2008
- Mitf regulation of Dia1 controls melanoma proliferation and invasivenessGenes & Development, 2006
- Identification of the Δ-6 Desaturase of Human Sebaceous Glands: Expression and Enzyme ActivityJournal of Investigative Dermatology, 2003
- A RAPID METHOD OF TOTAL LIPID EXTRACTION AND PURIFICATIONCanadian Journal of Biochemistry and Physiology, 1959