PUBLICATION
Circulating Tumor Cells Characterization Revealed TIMP1 as a Potential Therapeutic Target in Ovarian Cancer
- Authors
- Abreu, M., Cabezas-Sainz, P., Alonso-Alconada, L., Ferreirós, A., Mondelo-Macía, P., Lago-Lestón, R.M., Abalo, A., Díaz, E., Palacios-Zambrano, S., Rojo-Sebastian, A., López-López, R., Sánchez, L., Moreno-Bueno, G., Muinelo-Romay, L.
- ID
- ZDB-PUB-210225-7
- Date
- 2020
- Source
- Cells 9(5): (Journal)
- Registered Authors
- Keywords
- TIMP1, cell plasticity, circulating tumor cells (CTCs), ovarian cancer
- MeSH Terms
-
- Female
- Neoplastic Cells, Circulating/metabolism*
- Neoplastic Cells, Circulating/pathology*
- Gene Expression Regulation, Neoplastic
- Adult
- Cell Line, Tumor
- Aged
- Humans
- Aged, 80 and over
- Neoplasm Invasiveness
- Animals
- Middle Aged
- Mice
- Cell Plasticity
- Xenograft Model Antitumor Assays
- Young Adult
- Ovarian Neoplasms/diagnosis
- Ovarian Neoplasms/drug therapy*
- Ovarian Neoplasms/enzymology*
- Ovarian Neoplasms/genetics
- Tissue Inhibitor of Metalloproteinase-1/metabolism*
- Zebrafish
- Molecular Targeted Therapy*
- Down-Regulation
- Cell Proliferation
- PubMed
- 32423054 Full text @ Cells
Citation
Abreu, M., Cabezas-Sainz, P., Alonso-Alconada, L., Ferreirós, A., Mondelo-Macía, P., Lago-Lestón, R.M., Abalo, A., Díaz, E., Palacios-Zambrano, S., Rojo-Sebastian, A., López-López, R., Sánchez, L., Moreno-Bueno, G., Muinelo-Romay, L. (2020) Circulating Tumor Cells Characterization Revealed TIMP1 as a Potential Therapeutic Target in Ovarian Cancer. Cells. 9(5):.
Abstract
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 MUC1 and CK19, but also by genes associated with mesenchymal and more malignant features as TIMP1, CXCR4 and the stem markers CD24 and CD44. In addition, we evidenced the relevance of TIMP1 expression to promote tumor proliferation, suggesting its interest as a therapeutic target.
Conclusions Overall, we evidenced the utility of the molecular characterization of EpCAM+ CTCs from advanced ovarian cancer patients to identify biomarkers with potential applicability for disseminated disease detection and as therapeutic targets such as TIMP1.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping