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Updated: Jul 6, 2025
Quantitative Mass Spectrometric Profiling of Cancer-cell Proteomes Derived From Liquid and Solid Tumors
Published on: February 27, 2015
Investigating the Metabolic Heterogeneity of Cancer Cells Using Functional Single-Cell Selection and nLC Combined
Kai-Wen Cheng1, Pin-Rui Su1,2,3, Kate Jo-Ann Feller2,3
1Department of Chemistry, National Taiwan University, Taipei 10617, Taiwan.
Single-cell metabolomics reveals distinct lipid profiles in cancer cells, identifying specific fatty acids and ceramides linked to DNA damage response and cell migration, offering insights into tumor heterogeneity.
Area of Science:
- Cancer Research
- Metabolomics
- Cell Biology
Background:
- Tumor metastasis and recurrence are driven by cell heterogeneity.
- Subpopulations of cancer cells can exhibit resistance to therapies.
- Understanding cellular diversity is crucial for effective cancer treatment.
Purpose of the Study:
- To investigate physiological and phenotypic diversity in tumor cells using single-cell metabolomics.
- To establish a sensitive platform for in-depth single-cell lipid profiling.
- To identify distinct lipid profiles associated with specific cellular behaviors like DNA damage response and migration.
Main Methods:
- Developed a sensitive platform using nanoflow liquid chromatography (nLC) and multinozzle emitter electrospray ionization mass spectrometry.
- Analyzed lipid profiles of individual osteosarcoma (U2OS) and glioblastoma (GBM) cells.
- Utilized functional single-cell selection (fSCS) to isolate subpopulations with DNA damage response (DDR) or fast migration.
Main Results:
- Identified 15 and 17 distinct lipids from individual U2OS and GBM cells, respectively.
- Observed down-regulation of polyunsaturated fatty acids (PUFAs) in U2OS cells with DNA damage response.
- Found down-regulation of ceramides (Cer 38:0; O3) and triglycerides (TG 36:0) in fast-migrating GBM cells.
Conclusions:
- Single-cell metabolomics effectively differentiates tumor cell subpopulations based on lipid profiles.
- Specific lipids, including PUFAs, ceramides, and triglycerides, may play roles in cancer cell behavior.
- These findings contribute to understanding the chemical basis of tumor heterogeneity and therapeutic resistance.
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