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Effective Capture of Circulating Tumor Cells from a Transgenic Mouse Lung Cancer Model using Dendrimer Surfaces Immobilized with anti-EGFR Ja Hye Myung, Monic Roengvoraphoj, Kevin A. Tam, Tian Ma, Vincent A. Memoli, Ethan Dmitrovsky, Sarah J. Freemantle, and Seungpyo Hong Anal. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.analchem.5b02766 • Publication Date (Web): 27 Aug 2015 Downloaded from http://pubs.acs.org on August 28, 2015
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Analytical Chemistry
Effective Capture of Circulating Tumor Cells from a Transgenic Mouse Lung Cancer Model using Dendrimer Surfaces Immobilized with anti-EGFR Ja Hye Myung1, Monic Roengvoraphoj2, Kevin A. Tam1, Tian Ma3, Vincent A. Memoli4, Ethan Dmitrovsky2,3,5, Sarah J. Freemantle3, and Seungpyo Hong1,6* 1
Department of Biopharmaceutical Sciences, College of Pharmacy, The University of Illinois, Chicago, IL 60612 Department of Medicine, Dartmouth Hitchcock Medical Center, Lebanon, NH 03756 3 4 Departments of Pharmacology & Toxicology, and Pathology, Geisel School of Medicine, Dartmouth College, Hanover, NH 03753 5 Departments of Thoracic/Head and Neck Medical Oncology and Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030 6 Integrated Science and Engineering Division, Underwood International College, Yonsei University, Incheon, KOREA 406-840 2
ABSTRACT: The lack of an effective detection method for lung circulating tumor cells (CTCs) presents a substantial challenge to elucidate the value of CTCs as a diagnostic or prognostic indicator in lung cancer, particularly in non-small cell lung cancer (NSCLC). In this study, we prepared a capture surface exploiting strong multivalent binding mediated by poly(amidoamine) (PAMAM) dendrimers to capture CTCs originating from lung cancers. Given that 85% of the tumor cells from NSCLC patients overexpress epidermal growth factor receptor (EGFR), anti-EGFR was chosen as a capture agent. Following in vitro confirmation using the murine lung cancer cell lines (ED-1 and ED1-SC), cyclin Eoverexpressing (CEO) transgenic mice were employed as an in vivo lung tumor model to assess specificity and sensitivity of the capture surface. The numbers of CTCs in blood from the CEO transgenic mice were significantly higher than those from the healthy controls (on average 75.3 ± 14.9 vs. 4.4 ± 1.2 CTCs/100 µL of blood, p
