title: EpCAM-independent capture of circulating tumor cells with a 'universal CTC-chip'.
abstract: Capture of circulating tumor cells (CTCs), which are shed from the primary tumor site and circulate in the blood, remains a technical challenge. CellSearch® is the only clinically approved CTC detection system, but has provided only modest sensitivity in detecting CTCs mainly because epithelial cell adhesion molecule (EpCAM)-negative tumor cells may not be captured. To achieve more sensitive CTC‑capture, we have developed a novel microfluidic platform, a 'CTC-chip' comprised of light-curable resins that has a unique advantage in that any capture antibody is easily conjugated. In the present study, we showed that EpCAM-negative tumor cells as well as EpCAM-positive cells were captured with the novel 'universal CTC-chip' as follows: i) human lung cancer cells (PC-9), with strong EpCAM expression, were efficiently captured with the CTC-chip coated with an anti-EpCAM antibody (with an average capture efficiency of 101% when tumor cells were spiked in phosphate‑buffered saline (PBS) and 88% when spiked in blood); ii) human mesothelioma cells (ACC-MESO-4), with no EpCAM expression but with podoplanin expression, were captured with the CTC-chip coated with an anti-podoplanin antibody (average capture efficiency of 78% when tumor cells were spiked in PBS and 38% when spiked in blood), whereas ACC-MESO-4 cells were not captured with the CTC-chip coated with the anti-EpCAM antibody. These results indicate that the novel 'CTC-chip' can be useful in sensitive EpCAM-independent detection of CTCs, which may provide new insights into personalized medicine.
authors.affiliation: Second Department of Surgery, University of Occupational and Environmental Health, Kitakyushu, Fukuoka 807-8555, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Chikaishi
authors.affiliation: Second Department of Surgery, University of Occupational and Environmental Health, Kitakyushu, Fukuoka 807-8555, Japan.
authors.forename: Kazue
authors.initials: K
authors.lastname: Yoneda
authors.affiliation: Central Research Institute, Toyama Industrial Technology Center, Toyama 933-0981, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Ohnaga
authors.affiliation: Second Department of Surgery, University of Occupational and Environmental Health, Kitakyushu, Fukuoka 807-8555, Japan.
authors.forename: Fumihiro
authors.initials: F
authors.lastname: Tanaka
mesh_terms: D000951:Antigens, Neoplasm / Q000378:metabolism; D045744:Cell Line, Tumor; D002469:Cell Separation / Q000295:instrumentation* / Q000379:methods*; D000071858:Epithelial Cell Adhesion Molecule / Q000378:metabolism; D005434:Flow Cytometry / Q000295:instrumentation / Q000379:methods; D006801:Humans; D056656:Lab-On-A-Chip Devices; D008562:Membrane Glycoproteins / Q000378:metabolism; D046210:Microfluidic Analytical Techniques / Q000295:instrumentation / Q000379:methods; D009360:Neoplastic Cells, Circulating / Q000378:metabolism* / Q000473:pathology*; D000098853:Podoplanin
chemical_list: D000951:Antigens, Neoplasm; D000071858:Epithelial Cell Adhesion Molecule; D008562:Membrane Glycoproteins; C117468:PDPN protein, human; D000098853:Podoplanin