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Updated: Sep 7, 2025
Quantitative Mass Spectrometric Profiling of Cancer-cell Proteomes Derived From Liquid and Solid Tumors
Published on: February 27, 2015
Single-Cell Chemical Proteomics (SCCP) Interrogates the Timing and Heterogeneity of Cancer Cell Commitment to Death
Ákos Végvári1, Jimmy E Rodriguez1, Roman A Zubarev1
1Division of Physiological Chemistry I, Department of Medical Biochemistry & Biophysics, Karolinska Institutet, Biomedicum A9, Solnavägen 9, SE-171 77 Stockholm, Sweden.
Abstract:
Chemical proteomics studies the effects of drugs upon a cellular proteome. Due to the complexity and diversity of tumors, the response of cancer cells to drugs is also heterogeneous, and thus, proteome analysis at the single-cell level is needed. Here, we demonstrate that single-cell proteomics techniques have become quantitative enough to tackle the drug effects on target proteins, enabling single-cell chemical proteomics (SCCP). Using SCCP, we studied here the time-resolved response of individual adenocarcinoma A549 cells to anticancer drugs methotrexate, camptothecin, and tomudex, revealing the early emergence of cellular subpopulations committed and uncommitted to death. As a novel and useful approach to exploring the heterogeneous response to drugs of cancer cells, SCCP may prove to be a breakthrough application for single-cell proteomics.
Insights
Single-cell chemical proteomics (SCCP) now quantifies drug effects on cancer cells. This technique reveals distinct cell populations responding differently to anticancer drugs, offering new insights into tumor heterogeneity.
Area of Science:
- Proteomics
- Cancer Biology
- Pharmacology
Background:
- Tumor complexity leads to heterogeneous cellular responses to drugs.
- Proteome analysis at the single-cell level is crucial for understanding these heterogeneous responses.
- Existing techniques may lack the quantitative resolution for detailed drug effect studies.
Purpose of the Study:
- To demonstrate the capability of single-cell proteomics techniques for quantitative drug effect analysis.
- To introduce and validate single-cell chemical proteomics (SCCP) as a novel approach.
- To investigate the time-resolved cellular response to specific anticancer drugs.
Main Methods:
- Application of quantitative single-cell proteomics techniques.
- Development and implementation of single-cell chemical proteomics (SCCP).
- Time-resolved analysis of individual adenocarcinoma A549 cells treated with methotrexate, camptothecin, and tomudex.
Main Results:
- SCCP enables quantitative assessment of drug effects on target proteins at the single-cell level.
- Early emergence of distinct cellular subpopulations (committed and uncommitted to death) was observed.
- Heterogeneous cellular responses to anticancer drugs were detailed.
Conclusions:
- Single-cell chemical proteomics (SCCP) is a powerful new method for studying drug responses in cancer cells.
- SCCP provides insights into the heterogeneity of cancer cell drug responses.
- This technique holds promise for advancing single-cell proteomics applications in cancer research.
