title: Circulating tumour cells: the evolving concept and the inadequacy of their enrichment by EpCAM-based methodology for basic and clinical cancer research.
abstract: Increasing evidence suggests that circulating tumour cells (CTCs) are responsible for metastatic relapse and this has fuelled interest in their detection and quantification. Although numerous methods have been developed for the enrichment and detection of CTCs, none has yet reached the 'gold' standard. Since epithelial cell adhesion molecule (EpCAM)-based enrichment of CTCs offers several advantages, it is one of the most commonly used and has been adapted for high-throughput technology. However, emerging evidence suggests that CTCs are highly heterogeneous: they consist of epithelial tumour cells, epithelial-to-mesenchymal transition (EMT) cells, hybrid (epithelial/EMT(+)) tumour cells, irreversible EMT(+) tumour cells, and circulating tumour stem cells (CTSCs). The EpCAM-based approach does not detect CTCs expressing low levels of EpCAM and non-epithelial phenotypes such as CTSCs and those that have undergone EMT and no longer express EpCAM. Thus, the approach may lead to underestimation of the significance of CTCs, in general, and CTSCs and EMT(+) tumour cells, in particular, in cancer dissemination. Here, we provide a critical review of research literature on the evolving concept of CTCs and the inadequacy of their enrichment by EpCAM-based technology for basic and clinical cancer research. The review also outlines future perspectives in the field.
authors.affiliation: Departments of Surgery phulwindergrover@yahoo.com.
authors.forename: P K
authors.initials: PK
authors.lastname: Grover
authors.affiliation: Gastroenterology and Hepatology.
authors.forename: A G
authors.initials: AG
authors.lastname: Cummins
authors.affiliation: Haematology-Oncology, The Queen Elizabeth Hospital, Woodville South, Australia.
authors.forename: T J
authors.initials: TJ
authors.lastname: Price
authors.affiliation: Gastroenterology and Hepatology.
authors.forename: I C
authors.initials: IC
authors.lastname: Roberts-Thomson
authors.affiliation: Haematology-Oncology, The Queen Elizabeth Hospital, Woodville South, Australia.
authors.forename: J E
authors.initials: JE
authors.lastname: Hardingham
mesh_terms: D000951:Antigens, Neoplasm / Q000235:genetics / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D035843:Biomedical Research / Q000379:methods* / Q000592:standards*; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D002469:Cell Separation / Q000379:methods / Q000592:standards; D000071858:Epithelial Cell Adhesion Molecule; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009360:Neoplastic Cells, Circulating / Q000378:metabolism* / Q000473:pathology*; D010641:Phenotype
chemical_list: D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D015815:Cell Adhesion Molecules; C499379:EPCAM protein, human; D000071858:Epithelial Cell Adhesion Molecule
keywords: circulating EMT+ tumour cells; circulating cancer stem cells; circulating epithelial tumour cells; circulating hybrid tumour cells; circulating irreversible EMT+ tumour cells; circulating tumour cells