Circulating Tumor Cells Characterization Revealed TIMP1 as a Potential Therapeutic Target in Ovarian Cancer
Background: Recent studies showed a relevant role of hematogenous spread in ovarian cancer and the interest of circulating tumor cells (CTCs) monitoring as a prognosis marker. The aim of the present study was the characterization of CTCs from ovarian cancer patients, paying special attention to cell...
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MDPI AG
2020-05-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/9/5/1218 |
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| author | Manuel Abreu Pablo Cabezas-Sainz Lorena Alonso-Alconada Alba Ferreirós Patricia Mondelo-Macía Ramón Manuel Lago-Lestón Alicia Abalo Eva Díaz Sara Palacios-Zambrano Alejandro Rojo-Sebastian Rafael López-López Laura Sánchez Gema Moreno-Bueno Laura Muinelo-Romay |
| author_facet | Manuel Abreu Pablo Cabezas-Sainz Lorena Alonso-Alconada Alba Ferreirós Patricia Mondelo-Macía Ramón Manuel Lago-Lestón Alicia Abalo Eva Díaz Sara Palacios-Zambrano Alejandro Rojo-Sebastian Rafael López-López Laura Sánchez Gema Moreno-Bueno Laura Muinelo-Romay |
| author_sort | Manuel Abreu |
| collection | DOAJ |
| description | Background: Recent studies showed a relevant role of hematogenous spread in ovarian cancer and the interest of circulating tumor cells (CTCs) monitoring as a prognosis marker. The aim of the present study was the characterization of CTCs from ovarian cancer patients, paying special attention to cell plasticity characteristics to better understand the biology of these cells. Methods: CTCs isolation was carried out in 38 patients with advanced high-grade serous ovarian cancer using in parallel CellSearch and an alternative EpCAM-based immunoisolation followed by RT-qPCR analysis to characterize these cells. Results: Epithelial CTCs were found in 21% of patients, being their presence higher in patients with extraperitoneal metastasis. Importantly, this population was characterized by the expression of epithelial markers as <i>MUC1</i> and <i>CK19</i>, but also by genes associated with mesenchymal and more malignant features as <i>TIMP1, CXCR4</i> and the stem markers <i>CD24</i> and <i>CD44</i>. In addition, we evidenced the relevance of <i>TIMP1</i> expression to promote tumor proliferation, suggesting its interest as a therapeutic target. Conclusions: Overall, we evidenced the utility of the molecular characterization of EpCAM<sup>+</sup> CTCs from advanced ovarian cancer patients to identify biomarkers with potential applicability for disseminated disease detection and as therapeutic targets such as TIMP1. |
| first_indexed | 2024-03-10T19:49:55Z |
| format | Article |
| id | doaj.art-b738b9dde99b4c649e50f7a0c4e05e50 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T19:49:55Z |
| publishDate | 2020-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-b738b9dde99b4c649e50f7a0c4e05e502023-11-20T00:28:28ZengMDPI AGCells2073-44092020-05-0195121810.3390/cells9051218Circulating Tumor Cells Characterization Revealed TIMP1 as a Potential Therapeutic Target in Ovarian CancerManuel Abreu0Pablo Cabezas-Sainz1Lorena Alonso-Alconada2Alba Ferreirós3Patricia Mondelo-Macía4Ramón Manuel Lago-Lestón5Alicia Abalo6Eva Díaz7Sara Palacios-Zambrano8Alejandro Rojo-Sebastian9Rafael López-López10Laura Sánchez11Gema Moreno-Bueno12Laura Muinelo-Romay13Liquid Biopsy Analysis Unit, Translational Medical Oncology (Oncomet), Health Research Institute of Santiago (IDIS), 15706 Santiago de Compostela, SpainDepartment of Genetics, University of Santiago de Compostela, Campus de Lugo, 27002 Lugo, SpainNasasbiotech, S.L., Canton Grande 3, 15003 A Coruña, SpainNasasbiotech, S.L., Canton Grande 3, 15003 A Coruña, SpainLiquid Biopsy Analysis Unit, Translational Medical Oncology (Oncomet), Health Research Institute of Santiago (IDIS), 15706 Santiago de Compostela, SpainLiquid Biopsy Analysis Unit, Translational Medical Oncology (Oncomet), Health Research Institute of Santiago (IDIS), 15706 Santiago de Compostela, SpainLiquid Biopsy Analysis Unit, Translational Medical Oncology (Oncomet), Health Research Institute of Santiago (IDIS), 15706 Santiago de Compostela, SpainFundación MD Anderson Internacional, C/Gómez Hemans 2, 28033 Madrid, SpainMD Anderson Cancer Center, C/Arturo Soria 270, 28029 Madrid, SpainFundación MD Anderson Internacional, C/Gómez Hemans 2, 28033 Madrid, SpainTranslational Medical Oncology (Oncomet), Health Research Institute of Santiago de Compostela (IDIS), Complexo Hospitalario Universitario de Santiago de Compostela (SERGAS), 15706 Santiago de Compostela, SpainDepartment of Genetics, University of Santiago de Compostela, Campus de Lugo, 27002 Lugo, SpainFundación MD Anderson Internacional, C/Gómez Hemans 2, 28033 Madrid, SpainLiquid Biopsy Analysis Unit, Translational Medical Oncology (Oncomet), Health Research Institute of Santiago (IDIS), 15706 Santiago de Compostela, SpainBackground: Recent studies showed a relevant role of hematogenous spread in ovarian cancer and the interest of circulating tumor cells (CTCs) monitoring as a prognosis marker. The aim of the present study was the characterization of CTCs from ovarian cancer patients, paying special attention to cell plasticity characteristics to better understand the biology of these cells. Methods: CTCs isolation was carried out in 38 patients with advanced high-grade serous ovarian cancer using in parallel CellSearch and an alternative EpCAM-based immunoisolation followed by RT-qPCR analysis to characterize these cells. Results: Epithelial CTCs were found in 21% of patients, being their presence higher in patients with extraperitoneal metastasis. Importantly, this population was characterized by the expression of epithelial markers as <i>MUC1</i> and <i>CK19</i>, but also by genes associated with mesenchymal and more malignant features as <i>TIMP1, CXCR4</i> and the stem markers <i>CD24</i> and <i>CD44</i>. In addition, we evidenced the relevance of <i>TIMP1</i> expression to promote tumor proliferation, suggesting its interest as a therapeutic target. Conclusions: Overall, we evidenced the utility of the molecular characterization of EpCAM<sup>+</sup> CTCs from advanced ovarian cancer patients to identify biomarkers with potential applicability for disseminated disease detection and as therapeutic targets such as TIMP1.https://www.mdpi.com/2073-4409/9/5/1218ovarian cancercirculating tumor cells (CTCs)cell plasticityTIMP1 |
| spellingShingle | Manuel Abreu Pablo Cabezas-Sainz Lorena Alonso-Alconada Alba Ferreirós Patricia Mondelo-Macía Ramón Manuel Lago-Lestón Alicia Abalo Eva Díaz Sara Palacios-Zambrano Alejandro Rojo-Sebastian Rafael López-López Laura Sánchez Gema Moreno-Bueno Laura Muinelo-Romay Circulating Tumor Cells Characterization Revealed TIMP1 as a Potential Therapeutic Target in Ovarian Cancer Cells ovarian cancer circulating tumor cells (CTCs) cell plasticity TIMP1 |
| title | Circulating Tumor Cells Characterization Revealed TIMP1 as a Potential Therapeutic Target in Ovarian Cancer |
| title_full | Circulating Tumor Cells Characterization Revealed TIMP1 as a Potential Therapeutic Target in Ovarian Cancer |
| title_fullStr | Circulating Tumor Cells Characterization Revealed TIMP1 as a Potential Therapeutic Target in Ovarian Cancer |
| title_full_unstemmed | Circulating Tumor Cells Characterization Revealed TIMP1 as a Potential Therapeutic Target in Ovarian Cancer |
| title_short | Circulating Tumor Cells Characterization Revealed TIMP1 as a Potential Therapeutic Target in Ovarian Cancer |
| title_sort | circulating tumor cells characterization revealed timp1 as a potential therapeutic target in ovarian cancer |
| topic | ovarian cancer circulating tumor cells (CTCs) cell plasticity TIMP1 |
| url | https://www.mdpi.com/2073-4409/9/5/1218 |
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