title: Epithelial-to-mesenchymal transition leads to loss of EpCAM and different physical properties in circulating tumor cells from metastatic breast cancer.
abstract: 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.
authors.affiliation: School of Mechanical Engineering, Yonsei University, Seoul, Korea.
authors.forename: Kyung-A
authors.initials: KA
authors.lastname: Hyun
authors.affiliation: Department of Biochemistry, Ajou University School of Medicine, Suwon, Korea.|Department of Biomedical Sciences, Graduate School, Ajou University, Suwon, Korea.
authors.forename: Gi-Bang
authors.initials: GB
authors.lastname: Koo
authors.affiliation: Institute for Cancer Research, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Hyunju
authors.initials: H
authors.lastname: Han
authors.affiliation: Department of Medical Oncology, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Joohyuk
authors.initials: J
authors.lastname: Sohn
authors.affiliation: Department of Physics, Korea University, Seoul, Korea.
authors.forename: Wonshik
authors.initials: W
authors.lastname: Choi
authors.affiliation: Department of Surgery, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Seung-Il
authors.initials: SI
authors.lastname: Kim
authors.affiliation: School of Mechanical Engineering, Yonsei University, Seoul, Korea.
authors.forename: Hyo-Il
authors.initials: HI
authors.lastname: Jung
authors.affiliation: Department of Biochemistry, Ajou University School of Medicine, Suwon, Korea.|Department of Biomedical Sciences, Graduate School, Ajou University, Suwon, Korea.
authors.forename: You-Sun
authors.initials: YS
authors.lastname: Kim
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000071858:Epithelial Cell Adhesion Molecule / Q000235:genetics / Q000378:metabolism*; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D006801:Humans; D061986:MCF-7 Cells; D009362:Neoplasm Metastasis; D009360:Neoplastic Cells, Circulating / Q000378:metabolism* / Q000473:pathology
chemical_list: C499379:EPCAM protein, human; D000071858:Epithelial Cell Adhesion Molecule
keywords: EMT-induced breast cancer cell; EpCAM-negative; circulating tumor cells (CTCs); epithelial cell adhesion molecule (EpCAM); label-free separation