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Research ArticleExperimental Studies

Epithelial-to-mesenchymal Transition Heterogeneity of Circulating Tumor Cells and Their Correlation With MDSCs and Tregs in HER2-negative Metastatic Breast Cancer Patients

MARIA A. PAPADAKI, DESPOINA AGGOURAKI, ELENI-KYRIAKI VETSIKA, NIKOLAOS XENIDIS, GALAKTEA KALLERGI, ATHANASIOS KOTSAKIS and VASSILIS GEORGOULIAS
Anticancer Research February 2021, 41 (2) 661-670; DOI: https://doi.org/10.21873/anticanres.14817
MARIA A. PAPADAKI
1Laboratory of Translational Oncology, School of Medicine, University of Crete, Heraklion, Greece;
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DESPOINA AGGOURAKI
1Laboratory of Translational Oncology, School of Medicine, University of Crete, Heraklion, Greece;
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ELENI-KYRIAKI VETSIKA
1Laboratory of Translational Oncology, School of Medicine, University of Crete, Heraklion, Greece;
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NIKOLAOS XENIDIS
2Department of Medical Oncology, Medical School, Democritus University of Thrace, Alexandroupolis, Greece;
3Hellenic Oncology Research Group (HORG), Athens, Greece;
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GALAKTEA KALLERGI
3Hellenic Oncology Research Group (HORG), Athens, Greece;
4Department of Biology, University of Patras, Patras, Greece;
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ATHANASIOS KOTSAKIS
3Hellenic Oncology Research Group (HORG), Athens, Greece;
5Department of Medical Oncology, University Hospital of Larissa & Laboratory of Oncology, Faculty of Medicine, School of Health Sciences, University of Thessaly, Larissa, Greece;
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VASSILIS GEORGOULIAS
3Hellenic Oncology Research Group (HORG), Athens, Greece;
6School of Medicine, University of Crete, Heraklion, Greece
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  • For correspondence: georgulv{at}otenet.gr
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    Figure 1.

    Incidence of circulating immunosuppressive cells among mBC patients (n=38) and healthy volunteers (normal controls, NC; n=16). (A) Percentage of CD14+CD15+ M-MDSCs and CD14+CD15− M-MDSCs and CD14−CD15+ G-MDSCs. (B) Percentage of CD3+CD4+CD25high Tregs and CD3+CD4+CD25highFoxP3+ Tregs. The bars denote mean values±SEM and the p-values are determined by the Mann Whitney U-test.

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    Figure 2.

    ROS production and iNOS expression in different MDSCs’ subtypes. Percentages of (A) ROS-producing and (C) iNOS-expressing cells from normal donors (n=13) and mBC patients (n=38). Intracellular levels of (B) ROS and (D) iNOS in all tested subpopulations. Intracellular ROS levels are expressed as mean fluorescence intensity (MFI) in subpopulations of MDSCs before and after PMA stimulation. The data are represented as the mean±SEM and the p-values are determined by the Mann-Whitney U-test. ND: Normal donors.

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    Figure 3.

    Correlation between immunosuppressive cells and CTCs with distinct CSC and EMT phenotypes in mBC patients (n=38). Evaluation of the percentage of different immunosuppressive cell populations in the presence and absence of CTCs and within different CTC subpopulations. (A) Percentage of CD3+CD4+CD25high Tregs among CTC-positive and CTC-negative patients; (B) Percentage of CD14+CD15+ M-MDSCs among patients with and without CSC/partial-EMT CTCs; (C) Percentage of CD14+CD15– M-MDSCs and CD3+CD4+CD25high Tregs among patients with and without detectable non-CSC/epithelial CTCs. p-Values are determined by the Mann-Whitney U-test.

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Anticancer Research
Vol. 41, Issue 2
February 2021
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Epithelial-to-mesenchymal Transition Heterogeneity of Circulating Tumor Cells and Their Correlation With MDSCs and Tregs in HER2-negative Metastatic Breast Cancer Patients
MARIA A. PAPADAKI, DESPOINA AGGOURAKI, ELENI-KYRIAKI VETSIKA, NIKOLAOS XENIDIS, GALAKTEA KALLERGI, ATHANASIOS KOTSAKIS, VASSILIS GEORGOULIAS
Anticancer Research Feb 2021, 41 (2) 661-670; DOI: 10.21873/anticanres.14817

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Epithelial-to-mesenchymal Transition Heterogeneity of Circulating Tumor Cells and Their Correlation With MDSCs and Tregs in HER2-negative Metastatic Breast Cancer Patients
MARIA A. PAPADAKI, DESPOINA AGGOURAKI, ELENI-KYRIAKI VETSIKA, NIKOLAOS XENIDIS, GALAKTEA KALLERGI, ATHANASIOS KOTSAKIS, VASSILIS GEORGOULIAS
Anticancer Research Feb 2021, 41 (2) 661-670; DOI: 10.21873/anticanres.14817
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Keywords

  • CTC
  • MDSCs
  • Tregs
  • immune cells
  • Breast cancer
  • EMT
  • cancer stem cells
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