Effective capture of circulating tumor cells from a transgenic mouse lung cancer model using dendrimer surfaces immobilized with anti-EGFR.

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.

• Authors: Ja Hye Myung, Monic Roengvoraphoj, Kevin A Tam, Tian Ma, Vincent A Memoli, Ethan Dmitrovsky, Sarah J Freemantle, Seungpyo Hong
• Journal: Analytical chemistry (Anal Chem) Vol. 87 Issue 19 Pg. 10096-102 (Oct 06 2015) ISSN: 1520-6882 [Electronic] United States
• PMID: 26312815 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Antibodies, Immobilized
• Dendrimers
• Poly(amidoamine)
• Polyamines
• ErbB Receptors

Topics

• Animals
• Antibodies, Immobilized (chemistry)
• Carcinoma, Non-Small-Cell Lung (blood, diagnosis, pathology)
• Cell Count
• Cell Line, Tumor
• Cell Separation (methods)
• Dendrimers (chemistry)
• ErbB Receptors (analysis)
• Humans
• Lung Neoplasms (blood, diagnosis, pathology)
• Mice
• Mice, Transgenic
• Neoplastic Cells, Circulating (pathology)
• Polyamines (chemistry)
• Prognosis
• Surface Properties