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Updated: Aug 16, 2025
Studying Triple Negative Breast Cancer Using Orthotopic Breast Cancer Model
Published on: March 20, 2020
Single-cell protein profiling defines cell populations associated with triple-negative breast cancer aggressiveness
Barbora Kvokačková1,2,3, Radek Fedr1,2, Daniela Kužílková4,5
1Department of Cytokinetics, Institute of Biophysics of the Czech Academy of Sciences, Brno, Czech Republic.
Abstract:
Triple-negative breast cancer (TNBC) is an aggressive and complex subtype of breast cancer that lacks targeted therapy. TNBC manifests characteristic, extensive intratumoral heterogeneity that promotes disease progression and influences drug response. Single-cell techniques in combination with next-generation computation provide an unprecedented opportunity to identify molecular events with therapeutic potential. Here, we describe the generation of a comprehensive mass cytometry panel for multiparametric detection of 23 phenotypic markers and 13 signaling molecules. This single-cell proteomic approach allowed us to explore the landscape of TNBC heterogeneity, with particular emphasis on the tumor microenvironment. We prospectively profiled freshly resected tumors from 26 TNBC patients. These tumors contained phenotypically distinct subpopulations of cancer and stromal cells that were associated with the patient's clinical status at the time of surgery. We further classified the epithelial-mesenchymal plasticity of tumor cells, and molecularly defined phenotypically diverse populations of tumor-associated stroma. Furthermore, in a retrospective tissue-microarray TNBC cohort, we showed that the level of CD97 at the time of surgery has prognostic potential.
Insights
Triple-negative breast cancer (TNBC) exhibits significant heterogeneity, impacting treatment. This study used single-cell proteomics to map TNBC
Area of Science:
- Immunology
- Oncology
- Proteomics
Background:
- Triple-negative breast cancer (TNBC) is an aggressive subtype lacking targeted therapies.
- Intratumoral heterogeneity in TNBC drives disease progression and affects treatment response.
- Single-cell technologies offer novel avenues for identifying therapeutic targets in TNBC.
Purpose of the Study:
- To explore the heterogeneity of TNBC using a comprehensive single-cell proteomic approach.
- To characterize the tumor microenvironment and cellular subpopulations in TNBC.
- To identify potential prognostic markers for TNBC.
Main Methods:
- Generation of a mass cytometry panel for multiparametric detection of 23 phenotypic markers and 13 signaling molecules.
- Prospective profiling of freshly resected tumors from 26 TNBC patients using single-cell proteomics.
- Retrospective analysis of a TNBC tissue-microarray cohort.
Main Results:
- Identification of phenotypically distinct cancer and stromal cell subpopulations associated with clinical status.
- Classification of epithelial-mesenchymal plasticity in tumor cells.
- Molecular definition of diverse tumor-associated stroma populations.
- Demonstration of CD97 as a potential prognostic marker in TNBC.
Conclusions:
- Single-cell proteomics provides a detailed map of TNBC heterogeneity, including the tumor microenvironment.
- Distinct cellular subpopulations and their plasticity are linked to clinical status.
- CD97 expression levels may serve as a prognostic indicator for TNBC patients.
