Journal
ONCOTARGET
Volume 7, Issue 17, Pages 24677-24687Publisher
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.8250
Keywords
epithelial cell adhesion molecule (EpCAM); EpCAM-negative; EMT-induced breast cancer cell; circulating tumor cells (CTCs); label-free separation
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Funding
- National Research Foundation of Korea (NRF) - Korea government [2012R1A1A2008713, 2011-0030043]
- NRF - Korea government [2015R1A2A2A04006450]
- center for BioNano Health-Guard - Ministry of Science, ICT & Future Planning of Korea as a Global Frontier Project [H-GUARD_2013M3A6B2078959]
- National Research Foundation of Korea [2012R1A1A2008713, 2015R1A2A2A04006450] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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The dissemination of circulating tumor cells (CTCs) requires the Epithelial-to-Mesenchymal transition (EMT), in which cells lose their epithelial characteristics and acquire more mesenchymal-like phenotypes. Current isolation of CTCs relies on affinity-based approaches reliant on the expression of Epithelial Cell Adhesion Molecule (EpCAM). Here we show EMT-induced breast cancer cells maintained in prolonged mammosphere culture conditions possess increased EMT markers and cancer stem cell markers, as well as reduced cell mass and size by quantitative phase microscopy; however, EpCAM expression is dramatically decreased in these cells. Moreover, CTCs isolated from breast cancer patients using a label-free microfluidic flow fractionation device had differing expression patterns of EpCAM, indicating that affinity approaches reliant on EpCAM expression may underestimate CTC number and potentially miss critical subpopulations. Further characterization of CTCs, including low-EpCAM populations, using this technology may improve detection techniques and cancer diagnosis, ultimately improving cancer treatment.
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