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Biomed Microdevices (2012) 14:401407 DOI 10.1007/s10544-011-9616-5
Immunocapture of prostate cancer cells by use of anti-PSMA antibodies in microdevices
Steven M. Santana & He Liu & Neil H. Bander &
Jason P. Gleghorn & Brian J. Kirby
Published online: 6 December 2011# Springer Science+Business Media, LLC 2011
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 J415antibodies that are highly specific for intact extracellular domains of PSMA on live cellsin micro-fluidic 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.
Keywords CTC . Microfluidic . PSMA . J591 . Circulating tumor cell . Prostate cancer
AbbreviationsPCa Prostate CancerPCTC Prostate Circulating Tumor Cell CTC Circulating Tumor CellEpCAM Epithelial Cell Adhesion Molecule EMT Epithelial-to-Mesenchymal Transition PSMA Prostate Specific Membrane Antigen CRPC Castrate Resistant Prostate Cancer
1 Introduction
Patients suffering from metastatic prostate cancer (PCa) often shed tumor cells, called prostate circulating tumor cells (PCTCs), into the bloodstream (Allard et al. 2004; Danila et al. 2007). Although these PCTCs are rare and are
S. M. Santana : B. J. KirbySibley School of Mechanical and Aerospace Engineering, Cornell University,245 Upson Hall,Ithaca, NY 14853, USA
S. M. Santanae-mail: [email protected]: http://www.kirbyresearch.com/santana
H. Liu : N. H. BanderLaboratory of Urological Oncology,Weill Medical College of Cornell University, 1300 York Avenue, E-300,New York, NY 10065, USA
H. Liue-mail: [email protected]
N. H. Bandere-mail: [email protected]: http://weill.cornell.edu/research/researcher/neilhbander
J. P. GleghornSchool of Engineering and Applied Science, Department of Chemical and Biological Engineering, Princeton University, E-Quad A220, 59 Olden Street,Princeton, NJ 08544, USAe-mail: [email protected]