Circulating Tumor Cells Characterization Revealed TIMP1 as a Potential Therapeutic Target in Ovarian Cancer

被引：28

作者：

Abreu, Manuel ^{[1
]}

Cabezas-Sainz, Pablo ^{[2
]}

Alonso-Alconada, Lorena ^{[3
]}

Ferreiros, Alba ^{[3
]}

Mondelo-Macia, Patricia ^{[1
]}

Manuel Lago-Leston, Ramon ^{[1
]}

Abalo, Alicia ^{[1
]}

Diaz, Eva ^{[4
]}

Palacios-Zambrano, Sara ^{[5
]}

Rojo-Sebastian, Alejandro ^{[4
]}

Lopez-Lopez, Rafael ^{[6
,7
]}

Sanchez, Laura ^{[2
]}

Moreno-Bueno, Gema ^{[4
,7
,8
]}

Muinelo-Romay, Laura ^{[1
,8
]}

机构：

[1] Hlth Res Inst Santiago IDIS, Translat Med Oncol Oncomet, Liquid Biopsy Anal Unit, Santiago De Compostela 15706, Spain

[2] Univ Santiago Compostela, Dept Genet, Campus Lugo, Lugo 27002, Spain

[3] Nasasbiotech SL, Canton Grande 3, La Coruna 15003, Spain

[4] Fdn MD Anderson Internac, C Gomez Hemans 2, Madrid 28033, Spain

[5] MD Anderson Canc Ctr, C Arturo Soria 270, Madrid 28029, Spain

[6] Complexo Hosp Univ Santiago De Compostela SERGAS, Hlth Res Inst Santiago De Compostela IDIS, Translat Med Oncol Oncomet, Santiago De Compostela 15706, Spain

[7] Ctr Invest Biomed Red Canc CIBERONC, Monforte Lemos 3-5, Madrid 28029, Spain

[8] UAM, Dept Bioquim, Inst Invest Biomed Alberto Sols, CSIC,IdiPaz, Arzobispo Morcillo 4, Madrid 28029, Spain

来源：

CELLS | 2020年 / 9卷 / 05期

关键词：

ovarian cancer; circulating tumor cells (CTCs); cell plasticity; TIMP1; PROGNOSTIC RELEVANCE; TISSUE INHIBITOR; EXPRESSION; DIAGNOSIS; METALLOPROTEINASE-1; METASTASIS; CARCINOMA; MARKER; BLOOD;

D O I：

10.3390/cells9051218

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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.

引用

页数：19

共 42 条

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