Investigating the Role of CTCs with Stem/EMT-like Features in Metastatic Breast Cancer Patients Treated with Eribulin Mesylate
We herein aimed to assess the effect of eribulin mesylate on the cancer stem cell (CSC)/EMT-like phenotype of CTCs, and to investigate the prognostic role of CTC detection and monitoring for eribulin-treated BC patients. Peripheral blood was obtained at baseline (<i>n</i> = 42 patients)...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-08-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/14/16/3903 |
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| author | Maria A. Papadaki Anastasia Mala Aikaterini C. Merodoulaki Maria Vassilakopoulou Dimitrios Mavroudis Sofia Agelaki |
| author_facet | Maria A. Papadaki Anastasia Mala Aikaterini C. Merodoulaki Maria Vassilakopoulou Dimitrios Mavroudis Sofia Agelaki |
| author_sort | Maria A. Papadaki |
| collection | DOAJ |
| description | We herein aimed to assess the effect of eribulin mesylate on the cancer stem cell (CSC)/EMT-like phenotype of CTCs, and to investigate the prognostic role of CTC detection and monitoring for eribulin-treated BC patients. Peripheral blood was obtained at baseline (<i>n</i> = 42 patients) and 8 days after treatment initiation (C1D8: <i>n</i> = 22), and on disease progression (PD: <i>n</i> = 26). PBMCs cytospins were immunofluorescently stained for Cytokeratins/ALDH1/TWIST1/DAPI and analyzed via Ariol microscopy. CTCs were detected in 33.3%, 27.3%, and 23.1% of patients at baseline, C1D8, and PD, respectively. Accordingly, partial-EMT+ CTCs represented 61.3%, 0%, and 37.5% of total CTCs, whereas the CSC-like phenotype was consistently expressed by 87.5%, 75%, and 91.7% of CTCs at the respective time points. Interestingly, the CSC+/partial-EMT+ subset prevailed at baseline, but it was eradicated on C1D8 and resurged again during PD. CTC detection at baseline was associated with reduced PFS (<i>p</i> = 0.007) and OS (<i>p</i> = 0.005), and was an independent risk factor for death (HR: 3.779, <i>p</i> = 0.001; multivariate analysis). The CSC+/partial-EMT+ CTCs emerged as the only subset with adverse prognostic significance, while CTC monitoring during eribulin therapy improved the prediction of disease progression. These results indicate that resistant CTC subsets persevere eribulin treatment and highlight the prognostic implications of CTC analyses for eribulin-treated BC patients. |
| first_indexed | 2024-03-09T13:43:15Z |
| format | Article |
| id | doaj.art-6e181b5e494d4a6cace0967732355fb5 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-09T13:43:15Z |
| publishDate | 2022-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-6e181b5e494d4a6cace0967732355fb52023-11-30T21:03:59ZengMDPI AGCancers2072-66942022-08-011416390310.3390/cancers14163903Investigating the Role of CTCs with Stem/EMT-like Features in Metastatic Breast Cancer Patients Treated with Eribulin MesylateMaria A. Papadaki0Anastasia Mala1Aikaterini C. Merodoulaki2Maria Vassilakopoulou3Dimitrios Mavroudis4Sofia Agelaki5Laboratory of Translational Oncology, School of Medicine, University of Crete, 71003 Heraklion, GreeceLaboratory of Translational Oncology, School of Medicine, University of Crete, 71003 Heraklion, GreeceLaboratory of Translational Oncology, School of Medicine, University of Crete, 71003 Heraklion, GreeceLaboratory of Translational Oncology, School of Medicine, University of Crete, 71003 Heraklion, GreeceLaboratory of Translational Oncology, School of Medicine, University of Crete, 71003 Heraklion, GreeceLaboratory of Translational Oncology, School of Medicine, University of Crete, 71003 Heraklion, GreeceWe herein aimed to assess the effect of eribulin mesylate on the cancer stem cell (CSC)/EMT-like phenotype of CTCs, and to investigate the prognostic role of CTC detection and monitoring for eribulin-treated BC patients. Peripheral blood was obtained at baseline (<i>n</i> = 42 patients) and 8 days after treatment initiation (C1D8: <i>n</i> = 22), and on disease progression (PD: <i>n</i> = 26). PBMCs cytospins were immunofluorescently stained for Cytokeratins/ALDH1/TWIST1/DAPI and analyzed via Ariol microscopy. CTCs were detected in 33.3%, 27.3%, and 23.1% of patients at baseline, C1D8, and PD, respectively. Accordingly, partial-EMT+ CTCs represented 61.3%, 0%, and 37.5% of total CTCs, whereas the CSC-like phenotype was consistently expressed by 87.5%, 75%, and 91.7% of CTCs at the respective time points. Interestingly, the CSC+/partial-EMT+ subset prevailed at baseline, but it was eradicated on C1D8 and resurged again during PD. CTC detection at baseline was associated with reduced PFS (<i>p</i> = 0.007) and OS (<i>p</i> = 0.005), and was an independent risk factor for death (HR: 3.779, <i>p</i> = 0.001; multivariate analysis). The CSC+/partial-EMT+ CTCs emerged as the only subset with adverse prognostic significance, while CTC monitoring during eribulin therapy improved the prediction of disease progression. These results indicate that resistant CTC subsets persevere eribulin treatment and highlight the prognostic implications of CTC analyses for eribulin-treated BC patients.https://www.mdpi.com/2072-6694/14/16/3903eribulin mesylatecirculating tumor cells (CTCs)epithelial-to-mesenchymal transition (EMT)cancer stem cells (CSCs)liquid biopsybreast cancer |
| spellingShingle | Maria A. Papadaki Anastasia Mala Aikaterini C. Merodoulaki Maria Vassilakopoulou Dimitrios Mavroudis Sofia Agelaki Investigating the Role of CTCs with Stem/EMT-like Features in Metastatic Breast Cancer Patients Treated with Eribulin Mesylate Cancers eribulin mesylate circulating tumor cells (CTCs) epithelial-to-mesenchymal transition (EMT) cancer stem cells (CSCs) liquid biopsy breast cancer |
| title | Investigating the Role of CTCs with Stem/EMT-like Features in Metastatic Breast Cancer Patients Treated with Eribulin Mesylate |
| title_full | Investigating the Role of CTCs with Stem/EMT-like Features in Metastatic Breast Cancer Patients Treated with Eribulin Mesylate |
| title_fullStr | Investigating the Role of CTCs with Stem/EMT-like Features in Metastatic Breast Cancer Patients Treated with Eribulin Mesylate |
| title_full_unstemmed | Investigating the Role of CTCs with Stem/EMT-like Features in Metastatic Breast Cancer Patients Treated with Eribulin Mesylate |
| title_short | Investigating the Role of CTCs with Stem/EMT-like Features in Metastatic Breast Cancer Patients Treated with Eribulin Mesylate |
| title_sort | investigating the role of ctcs with stem emt like features in metastatic breast cancer patients treated with eribulin mesylate |
| topic | eribulin mesylate circulating tumor cells (CTCs) epithelial-to-mesenchymal transition (EMT) cancer stem cells (CSCs) liquid biopsy breast cancer |
| url | https://www.mdpi.com/2072-6694/14/16/3903 |
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