Effective Capture of Circulating Tumor Cells from a Transgenic Mouse Lung Cancer Model using...

Effective Capture of Circulating Tumor Cells from a Transgenic Mouse Lung Cancer Model using Dendrimer Surfaces Immobilized with anti-EGFR

Ja Hye Myung,1 Monic Roengvoraphoj,2 Kevin A. Tam,1 Tian Ma,3 Vincent A. Memoli,4 Ethan Dmitrovsky,2,3,5 Sarah J. Freemantle,3 and Seungpyo Hong1,6,*

1 Department of Biopharmaceutical Sciences, College of Pharmacy, The University of Illinois, Chicago, Illinois 60612, United States.

2 Department of Medicine, Dartmouth Hitchcock Medical Center , Lebanon, New Hampshire 03756, United States.

3 Departments of Thoracic/Head and Neck Medical Oncology and Cancer Biology, The University of Texas MD Anderson Cancer Center , Houston, Texas 77030, United States.

4 Integrated Science and Engineering Division, Underwood International College, Yonsei University , Incheon 406-840, Korea.

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 nonsmall 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 E-overexpressing (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 < 0.005), indicating the high sensitivity and specificity of our surface. Furthermore, we found that the capture surface also offers a simple, effective method for monitoring treatment responses, as observed by the significant decrease in the CTC numbers from the CEO mice upon a treatment using a novel anti-miR-31 locked nucleic acid (LNA), compared to a vehicle treatment and a control-LNA treatment (p < 0.05). This in vivo evaluation study confirms that our capture surface is highly efficient in detecting in vivo CTCs and thus has translational potential as a diagnostic and prognostic tool for lung cancer.