Advanced Technologies for Studying Circulating Tumor Cells at the Protein Level

Charles Ming Lok Chan; Thomas Chi Chuen Au; Anthony Tak Cheung Chan; Brigette Buig Yue Ma; Nancy Bo Yin Tsui; Simon Siu Man Ng; Edwin Pun Hui; Lawrence Wing Chi Chan; Wing Shan Ho; Benjamin Yat Ming Yung; Sze Chuen Cesar Wong

Disclosures

Expert Rev Proteomics. 2013;10(6):579-589.

Protein Markers Used in CTC Investigations

EpCAM

EpCAM, also known as HEA or BerEP4, is commonly expressed by many epithelial cells but not in blood cells, adult squamous epithelium, hepatocytes, myoepithelia and mesothelia cells or fibroblasts.^[17–19] It has been reported that up to 95% of epithelial tumors express this antigen but is usually not expressed in hepatocellular carcinoma, squamous carcinoma of the skin or mesotheliomas.^[20–22] EpCAM is one of the most commonly used markers for the positive isolation and detection of CTCs from patient blood. It is used for CTC isolation in CellSearch®, CTC-Chip and immunomagnetic beads such as MACS® and Dynabeads® (discussed below). However, not all tumors, including those from epithelial or non-epithelial origin, express EpCAM, such as renal cell carcinoma and melanoma. Its expression level also varies across different cancer types which express this marker. Another limitation of using this marker is that the occurrence of epithelial-mesenchymal transition (EMT) in tumor cells lead to downregulation of epithelial markers including EpCAM and reduces the sensitivity for detection of CTC.^[23,24]

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Abstract and Introduction
Protein Markers Used in CTC Investigations
Cytokeratins
Technologies for CTC Detection Using Protein Markers
Immunomagnetic Beads
Epithelial Immunospot
Other Methods for Isolation & Investigation of CTCs
Expert Commentary & Five-year View
References
Sidebar

Table 1. Protein markers commonly used for circulating tumor cells investigations.
Target protein	Examples of cell/tissue types which express this protein	Ref.
EpCAM (also called HEA or BerEP4)	Epithelial cells such as breast, lung and colon	[17–19]
Cytokeratins (e.g., CK8, CK18, CK19)	Epithelial cells such as breast, lung and colon	[27–29]
Mucin 1	Colon, lung, breast, ovarian, pancreatic, prostate, kidney, stomach, head and neck	[37–40]
HER2	Breast	[5,46–55]
CD45	Hematopoietic cells	[56–61]
CD133	Stem cells from hematopoietic cells, brain, prostate liver, pancreas, lung colon and ovary	[62–73]
Chemokine receptors (e.g., CXCR4, CCR6, CCR7, CCR9)	Stomach, lung, kidney, colon, breast	[86–91]
Adhesion molecules (e.g., VCAM-1, ICAM-1)	Endothelial cells, skin, pancreas, breast	[93–99]