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Fusion Cell Markers in Circulating Tumor Cells from Patients with High-Grade Ovarian Serous Carcinoma
Cancer is primarily a disease in which late diagnosis is linked to poor prognosis, and unfortunately, detection and management are still challenging. Circulating tumor cells (CTCs) are a potential resource to address this disease. Cell fusion, an event discovered recently in CTCs expressing carcinom...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9740150/ https://www.ncbi.nlm.nih.gov/pubmed/36499015 http://dx.doi.org/10.3390/ijms232314687 |
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author | Ruano, Anna Paula Carreta Gadelha Guimarães, Andrea Paiva Braun, Alexcia C. Flores, Bianca C. T. C. P. Tariki, Milena Shizue Abdallah, Emne A. Torres, Jacqueline Aparecida Nunes, Diana Noronha Tirapelli, Bruna de Lima, Vladmir C. Cordeiro Fanelli, Marcello Ferretti Colombo, Pierre-Emmanuel da Costa, Alexandre André Balieiro Anastácio Alix-Panabières, Catherine Chinen, Ludmilla Thomé Domingos |
author_facet | Ruano, Anna Paula Carreta Gadelha Guimarães, Andrea Paiva Braun, Alexcia C. Flores, Bianca C. T. C. P. Tariki, Milena Shizue Abdallah, Emne A. Torres, Jacqueline Aparecida Nunes, Diana Noronha Tirapelli, Bruna de Lima, Vladmir C. Cordeiro Fanelli, Marcello Ferretti Colombo, Pierre-Emmanuel da Costa, Alexandre André Balieiro Anastácio Alix-Panabières, Catherine Chinen, Ludmilla Thomé Domingos |
author_sort | Ruano, Anna Paula Carreta |
collection | PubMed |
description | Cancer is primarily a disease in which late diagnosis is linked to poor prognosis, and unfortunately, detection and management are still challenging. Circulating tumor cells (CTCs) are a potential resource to address this disease. Cell fusion, an event discovered recently in CTCs expressing carcinoma and leukocyte markers, occurs when ≥2 cells become a single entity (hybrid cell) after the merging of their plasma membranes. Cell fusion is still poorly understood despite continuous evaluations in in vitro/in vivo studies. Blood samples from 14 patients with high-grade serous ovarian cancer (A.C. Camargo Cancer Center, São Paulo, Brazil) were collected with the aim to analyze the CTCs/hybrid cells and their correlation to clinical outcome. The EDTA collected blood (6 mL) from patients was used to isolate/identify CTCs/hybrid cells by ISET. We used markers with possible correlation with the phenomenon of cell fusion, such as MC1-R, EpCAM and CD45, as well as CEN8 expression by CISH analysis. Samples were collected at three timepoints: baseline, after one month (first follow-up) and after three months (second follow-up) of treatment with olaparib (total sample = 38). Fourteen patients were included and in baseline and first follow-up all patients showed at least one CTC. We found expression of MC1-R, EpCAM and CD45 in cells (hybrid) in at least one of the collection moments. Membrane staining with CD45 was found in CTCs from the other cohort, from the other center, evaluated by the CellSearch(®) system. The presence of circulating tumor microemboli (CTM) in the first follow-up was associated with a poor recurrence-free survival (RFS) (5.2 vs. 12.2 months; p = 0.005). The MC1-R expression in CTM in the first and second follow-ups was associated with a shorter RFS (p = 0.005). CEN8 expression in CTCs was also related to shorter RFS (p = 0.035). Our study identified a high prevalence of CTCs in ovarian cancer patients, as well as hybrid cells. Both cell subtypes demonstrate utility in prognosis and in the assessment of response to treatment. In addition, the expression of MC1-R and EpCAM in hybrid cells brings new perspectives as a possible marker for this phenomenon in ovarian cancer. |
format | Online Article Text |
id | pubmed-9740150 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-97401502022-12-11 Fusion Cell Markers in Circulating Tumor Cells from Patients with High-Grade Ovarian Serous Carcinoma Ruano, Anna Paula Carreta Gadelha Guimarães, Andrea Paiva Braun, Alexcia C. Flores, Bianca C. T. C. P. Tariki, Milena Shizue Abdallah, Emne A. Torres, Jacqueline Aparecida Nunes, Diana Noronha Tirapelli, Bruna de Lima, Vladmir C. Cordeiro Fanelli, Marcello Ferretti Colombo, Pierre-Emmanuel da Costa, Alexandre André Balieiro Anastácio Alix-Panabières, Catherine Chinen, Ludmilla Thomé Domingos Int J Mol Sci Article Cancer is primarily a disease in which late diagnosis is linked to poor prognosis, and unfortunately, detection and management are still challenging. Circulating tumor cells (CTCs) are a potential resource to address this disease. Cell fusion, an event discovered recently in CTCs expressing carcinoma and leukocyte markers, occurs when ≥2 cells become a single entity (hybrid cell) after the merging of their plasma membranes. Cell fusion is still poorly understood despite continuous evaluations in in vitro/in vivo studies. Blood samples from 14 patients with high-grade serous ovarian cancer (A.C. Camargo Cancer Center, São Paulo, Brazil) were collected with the aim to analyze the CTCs/hybrid cells and their correlation to clinical outcome. The EDTA collected blood (6 mL) from patients was used to isolate/identify CTCs/hybrid cells by ISET. We used markers with possible correlation with the phenomenon of cell fusion, such as MC1-R, EpCAM and CD45, as well as CEN8 expression by CISH analysis. Samples were collected at three timepoints: baseline, after one month (first follow-up) and after three months (second follow-up) of treatment with olaparib (total sample = 38). Fourteen patients were included and in baseline and first follow-up all patients showed at least one CTC. We found expression of MC1-R, EpCAM and CD45 in cells (hybrid) in at least one of the collection moments. Membrane staining with CD45 was found in CTCs from the other cohort, from the other center, evaluated by the CellSearch(®) system. The presence of circulating tumor microemboli (CTM) in the first follow-up was associated with a poor recurrence-free survival (RFS) (5.2 vs. 12.2 months; p = 0.005). The MC1-R expression in CTM in the first and second follow-ups was associated with a shorter RFS (p = 0.005). CEN8 expression in CTCs was also related to shorter RFS (p = 0.035). Our study identified a high prevalence of CTCs in ovarian cancer patients, as well as hybrid cells. Both cell subtypes demonstrate utility in prognosis and in the assessment of response to treatment. In addition, the expression of MC1-R and EpCAM in hybrid cells brings new perspectives as a possible marker for this phenomenon in ovarian cancer. MDPI 2022-11-24 /pmc/articles/PMC9740150/ /pubmed/36499015 http://dx.doi.org/10.3390/ijms232314687 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Ruano, Anna Paula Carreta Gadelha Guimarães, Andrea Paiva Braun, Alexcia C. Flores, Bianca C. T. C. P. Tariki, Milena Shizue Abdallah, Emne A. Torres, Jacqueline Aparecida Nunes, Diana Noronha Tirapelli, Bruna de Lima, Vladmir C. Cordeiro Fanelli, Marcello Ferretti Colombo, Pierre-Emmanuel da Costa, Alexandre André Balieiro Anastácio Alix-Panabières, Catherine Chinen, Ludmilla Thomé Domingos Fusion Cell Markers in Circulating Tumor Cells from Patients with High-Grade Ovarian Serous Carcinoma |
title | Fusion Cell Markers in Circulating Tumor Cells from Patients with High-Grade Ovarian Serous Carcinoma |
title_full | Fusion Cell Markers in Circulating Tumor Cells from Patients with High-Grade Ovarian Serous Carcinoma |
title_fullStr | Fusion Cell Markers in Circulating Tumor Cells from Patients with High-Grade Ovarian Serous Carcinoma |
title_full_unstemmed | Fusion Cell Markers in Circulating Tumor Cells from Patients with High-Grade Ovarian Serous Carcinoma |
title_short | Fusion Cell Markers in Circulating Tumor Cells from Patients with High-Grade Ovarian Serous Carcinoma |
title_sort | fusion cell markers in circulating tumor cells from patients with high-grade ovarian serous carcinoma |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9740150/ https://www.ncbi.nlm.nih.gov/pubmed/36499015 http://dx.doi.org/10.3390/ijms232314687 |
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