Improved ovarian cancer EMT-CTC isolation by immunomagnetic targeting of epithelial EpCAM and mesenchymal N-cadherin.

Autor:	Po JW; Centre for Circulating Tumour Cell Diagnostics and Research, Ingham Institute for Applied Medical Research, Liverpool, New South Wales, Australia.; School of Medicine, Western Sydney University, Campbelltown, New South Wales, Australia., Roohullah A; Centre for Circulating Tumour Cell Diagnostics and Research, Ingham Institute for Applied Medical Research, Liverpool, New South Wales, Australia.; School of Medicine, Western Sydney University, Campbelltown, New South Wales, Australia.; Department of Medical Oncology, Liverpool Hospital, Liverpool, New South Wales, Australia., Lynch D; Centre for Circulating Tumour Cell Diagnostics and Research, Ingham Institute for Applied Medical Research, Liverpool, New South Wales, Australia.; School of Medicine, Western Sydney University, Campbelltown, New South Wales, Australia., DeFazio A; Centre for Cancer Research, Westmead Institute for Medical Research, Westmead, New South Wales, Australia.; The University of Sydney, New South Wales, Australia.; The Crown Princess Mary Cancer Centre Westmead, Westmead Hospital, New South Wales, Australia., Harrison M; Department of Medical Oncology, Liverpool Hospital, Liverpool, New South Wales, Australia.; Department of Medical Oncology, Chris O'Brien Lifehouse, Camperdown, New South Wales, Australia., Harnett PR; Centre for Cancer Research, Westmead Institute for Medical Research, Westmead, New South Wales, Australia.; The University of Sydney, New South Wales, Australia.; The Crown Princess Mary Cancer Centre Westmead, Westmead Hospital, New South Wales, Australia., Kennedy C; Centre for Cancer Research, Westmead Institute for Medical Research, Westmead, New South Wales, Australia.; The University of Sydney, New South Wales, Australia.; The Crown Princess Mary Cancer Centre Westmead, Westmead Hospital, New South Wales, Australia., de Souza P; Centre for Circulating Tumour Cell Diagnostics and Research, Ingham Institute for Applied Medical Research, Liverpool, New South Wales, Australia.; School of Medicine, Western Sydney University, Campbelltown, New South Wales, Australia.; Department of Medical Oncology, Liverpool Hospital, Liverpool, New South Wales, Australia.; South Western Clinical School, University of New South Wales, Liverpool, New South Wales, Australia., Becker TM; Centre for Circulating Tumour Cell Diagnostics and Research, Ingham Institute for Applied Medical Research, Liverpool, New South Wales, Australia.; School of Medicine, Western Sydney University, Campbelltown, New South Wales, Australia.; Centre for Cancer Research, Westmead Institute for Medical Research, Westmead, New South Wales, Australia.; South Western Clinical School, University of New South Wales, Liverpool, New South Wales, Australia.
Jazyk:	angličtina
Zdroj:	Journal of circulating biomarkers [J Circ Biomark] 2018 Jun 24; Vol. 7, pp. 1849454418782617. Date of Electronic Publication: 2018 Jun 24 (Print Publication: 2018).
DOI:	10.1177/1849454418782617
Abstrakt:	Epithelial cell adhesion molecule (EpCAM)-targeted capture remains the most common isolation strategy for circulating tumor cells (CTCs). However, epithelial-to-mesenchymal transition (EMT) leads to decreased epithelial EpCAM expression affecting the optimal CTC capture. In this study, we tested a cohort of ovarian cancer cell lines using flow cytometry to identify N-cadherin as the additional immunomagnetic cell surface target for ovarian cancer cell isolation. Combined immunomagnetic targeting of mesenchymal N-cadherin and epithelial EpCAM enriched CTCs from advanced ovarian cancer patient blood approximately three times more efficiently than targeting of EpCAM alone. We also show that more EMT-phenotype CTCs are captured by including N-cadherin targeting into CTC isolation protocols. However, after N-cadherin-based CTC isolation, in some blood samples of healthy individuals, we also observed the presence of cells expressing markers common to CTCs. Our data show that these "false positives" can be largely distinguished from CTCs as circulating endothelial cells (CECs) by vascular endothelial-cadherin co-staining. CEC counts are highly variable in patients and healthy controls. Our data demonstrate that a combination of EpCAM with N-cadherin-targeted isolation can improve CTC detection and widen the EMT-phenotype spectrum of captured CTCs. Competing Interests: Declaration of Conflicting Interests: The author/s declared no conflicts of interest with respect to the research, authorship, and/or publication of this article.
Databáze:	MEDLINE
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