title: Immunocapture of prostate cancer cells by use of anti-PSMA antibodies in microdevices.
abstract: Patients suffering from cancer can shed tumor cells into the bloodstream, leading to one of the most important mechanisms of metastasis. As such, the capture of these cells is of great interest. Circulating tumor cells are typically extracted from circulation through positive selection with the epithelial cell-adhesion molecule (EpCAM), leading to currently unknown biases when cells are undergoing epithelial-to-mesenchymal transition. For prostate cancer, prostate-specific membrane antigen (PSMA) presents a compelling target for immunocapture, as PSMA levels increase in higher-grade cancers and metastatic disease and are specific to the prostate epithelium. This study uses monoclonal antibodies J591 and J415-antibodies that are highly specific for intact extracellular domains of PSMA on live cells-in microfluidic devices for the capture of LNCaPs, a PSMA-expressing immortalized prostate cancer cell line, over a range of concentrations and shear stresses relevant to immunocapture. Our results show that J591 outperforms J415 and a mix of the two for prostate cancer capture, and that capture performance saturates following incubation with antibody concentrations of 10 micrograms per milliliter.
authors.affiliation: Sibley School of Mechanical and Aerospace Engineering, Cornell University, 245 Upson Hall, Ithaca, NY 14853, USA. sms492@cornell.edu
authors.forename: Steven M
authors.initials: SM
authors.lastname: Santana
authors.forename: He
authors.initials: H
authors.lastname: Liu
authors.forename: Neil H
authors.initials: NH
authors.lastname: Bander
authors.forename: Jason P
authors.initials: JP
authors.lastname: Gleghorn
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Kirby
mesh_terms: D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm / Q000378:metabolism; D000954:Antigens, Surface / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000378:metabolism; D045744:Cell Line, Tumor; D000071858:Epithelial Cell Adhesion Molecule; D004867:Equipment Design; D043425:Glutamate Carboxypeptidase II / Q000378:metabolism*; D006801:Humans; D008297:Male; D046210:Microfluidic Analytical Techniques / Q000295:instrumentation / Q000379:methods*; D009360:Neoplastic Cells, Circulating; D011471:Prostatic Neoplasms / Q000473:pathology*
chemical_list: D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D000954:Antigens, Surface; D015815:Cell Adhesion Molecules; D000071858:Epithelial Cell Adhesion Molecule; C478680:J591 monoclonal antibody; C473848:FOLH1 protein, human; D043425:Glutamate Carboxypeptidase II