2023
Kvokačková, Barbora; Fedr, Radek; Kužílková, Daniela; Stuchlý, Jan; Vávrová, Adéla; Navrátil, Jiří; Fabian, Pavel; Ondruššek, Róbert; Ovesná, Petra; Remšík, Ján; Bouchal, Jan; Kalina, Tomáš; Souček, Karel
Single-cell protein profiling defines cell populations associated with triple-negative breast cancer aggressiveness. Journal Article
In: Molecular oncology, vol. 17, no. 6, pp. 1024–1040, 2023, ISSN: 1878-0261 1574-7891, (Place: United States).
Abstract | Links | BibTeX | Tags: *Triple Negative Breast Neoplasms/metabolism, Cell Line, Humans, mass cytometry, phenotypic plasticity, Proteomics, Retrospective Studies, Signal Transduction, single-cell profiles, Stromal Cells/metabolism, triple-negative breast cancer, Tumor, tumor heterogeneity, Tumor microenvironment, unsupervised machine learning algorithm
@article{kvokackova_single-cell_2023,
title = {Single-cell protein profiling defines cell populations associated with triple-negative breast cancer aggressiveness.},
author = {Barbora Kvokačková and Radek Fedr and Daniela Kužílková and Jan Stuchlý and Adéla Vávrová and Jiří Navrátil and Pavel Fabian and Róbert Ondruššek and Petra Ovesná and Ján Remšík and Jan Bouchal and Tomáš Kalina and Karel Souček},
doi = {10.1002/1878-0261.13365},
issn = {1878-0261 1574-7891},
year = {2023},
date = {2023-06-01},
journal = {Molecular oncology},
volume = {17},
number = {6},
pages = {1024–1040},
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.},
note = {Place: United States},
keywords = {*Triple Negative Breast Neoplasms/metabolism, Cell Line, Humans, mass cytometry, phenotypic plasticity, Proteomics, Retrospective Studies, Signal Transduction, single-cell profiles, Stromal Cells/metabolism, triple-negative breast cancer, Tumor, tumor heterogeneity, Tumor microenvironment, unsupervised machine learning algorithm},
pubstate = {published},
tppubtype = {article}
}
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.
2021
Kvokačková, Barbora; Remšík, Ján; Jolly, Mohit Kumar; Souček, Karel
Phenotypic Heterogeneity of Triple-Negative Breast Cancer Mediated by Epithelial-Mesenchymal Plasticity. Journal Article
In: Cancers, vol. 13, no. 9, 2021, ISSN: 2072-6694, (Place: Switzerland).
Abstract | Links | BibTeX | Tags: epithelial–mesenchymal transition, mesenchymal–epithelial transition, Metastasis, Plasticity, triple-negative breast cancer
@article{kvokackova_phenotypic_2021,
title = {Phenotypic Heterogeneity of Triple-Negative Breast Cancer Mediated by Epithelial-Mesenchymal Plasticity.},
author = {Barbora Kvokačková and Ján Remšík and Mohit Kumar Jolly and Karel Souček},
doi = {10.3390/cancers13092188},
issn = {2072-6694},
year = {2021},
date = {2021-05-01},
journal = {Cancers},
volume = {13},
number = {9},
abstract = {Triple-negative breast cancer (TNBC) is a subtype of breast carcinoma known for its unusually aggressive behavior and poor clinical outcome. Besides the lack of molecular targets for therapy and profound intratumoral heterogeneity, the relatively quick overt metastatic spread remains a major obstacle in effective clinical management. The metastatic colonization of distant sites by primary tumor cells is affected by the microenvironment, epigenetic state of particular subclones, and numerous other factors. One of the most prominent processes contributing to the intratumoral heterogeneity is an epithelial-mesenchymal transition (EMT), an evolutionarily conserved developmental program frequently hijacked by tumor cells, strengthening their motile and invasive features. In response to various intrinsic and extrinsic stimuli, malignant cells can revert the EMT state through the mesenchymal-epithelial transition (MET), a process that is believed to be critical for the establishment of macrometastasis at secondary sites. Notably, cancer cells rarely undergo complete EMT and rather exist in a continuum of E/M intermediate states, preserving high levels of plasticity, as demonstrated in primary tumors and, ultimately, in circulating tumor cells, representing a simplified element of the metastatic cascade. In this review, we focus on cellular drivers underlying EMT/MET phenotypic plasticity and its detrimental consequences in the context of TNBC cancer.},
note = {Place: Switzerland},
keywords = {epithelial–mesenchymal transition, mesenchymal–epithelial transition, Metastasis, Plasticity, triple-negative breast cancer},
pubstate = {published},
tppubtype = {article}
}
Triple-negative breast cancer (TNBC) is a subtype of breast carcinoma known for its unusually aggressive behavior and poor clinical outcome. Besides the lack of molecular targets for therapy and profound intratumoral heterogeneity, the relatively quick overt metastatic spread remains a major obstacle in effective clinical management. The metastatic colonization of distant sites by primary tumor cells is affected by the microenvironment, epigenetic state of particular subclones, and numerous other factors. One of the most prominent processes contributing to the intratumoral heterogeneity is an epithelial-mesenchymal transition (EMT), an evolutionarily conserved developmental program frequently hijacked by tumor cells, strengthening their motile and invasive features. In response to various intrinsic and extrinsic stimuli, malignant cells can revert the EMT state through the mesenchymal-epithelial transition (MET), a process that is believed to be critical for the establishment of macrometastasis at secondary sites. Notably, cancer cells rarely undergo complete EMT and rather exist in a continuum of E/M intermediate states, preserving high levels of plasticity, as demonstrated in primary tumors and, ultimately, in circulating tumor cells, representing a simplified element of the metastatic cascade. In this review, we focus on cellular drivers underlying EMT/MET phenotypic plasticity and its detrimental consequences in the context of TNBC cancer.