Raman spectroscopy of isogenic breast cancer cells derived from organ-specific metastases reveals distinct biochemical signatures

Recorded On: 02/07/2018

Objective characterization of the biomolecular divergences of metastatic lesions, which distinguish them from the primary tumor, remains challenging but is crucial for better understanding of organ-specific adaptations that regulate metastatic progression. Using an orthotopic xenograft model, we have isolated isogenic metastatic human breast cancer cells directly from organ explants that show phenotypic differences from the primary tumor cell line. Leveraging label-free Raman spectroscopic measurements on these isogenic metastatic breast cancer cells from the brain, spine, lung and liver, we designed decision algorithms to enable accurate differentiation without requiring staining or human interpretation. The Raman spectroscopy-based decision models show significant diagnostic power in resolving these isogenic cell lines by analyzing the nucleic acid, protein, lipid and metabolite content. The latter differences were validated through metabolomic analyses that revealed tissue of origin distinctions between the cell lines. Our findings provide evidence that metastatic spread generates tissue-specific adaptations at the molecular level within cancer cells, and open the door for use of Raman spectroscopy to define organ-specific smart chemotherapeutic approaches.

Chi Zhang

Johns Hopkins University

Mr. Chi Zhang is a Ph.D candidate in Mechanical Engineering, Johns Hopkins University. His current research efforts in Dr. Ishan Barman’s lab are directed towards application of Raman spectroscopy and multivariate data analysis to develop novel quantitative approaches for addressing unmet needs in the biochemical study of cancers. He recent mainly focuses on breast cancer cell biochemical and biomechanical variances diagnosis during metastasis by using Raman spectroscopy and machine learning techniques. He also works on kidney stone identification and otitis media effusion analysis. He has published five papers in journals such as Analytical chemistry and Accounts of Chemical Research. He has been awarded the Whiting School Doctoral Fellowship and Mechanical Engineering Departmental Fellowship by Johns Hopkins University.

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