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Effective capture of circulating tumor cells from a transgenic mouse lung cancer model using dendrimer surfaces immobilized with anti-EGFR.
- Source :
-
Analytical chemistry [Anal Chem] 2015 Oct 06; Vol. 87 (19), pp. 10096-102. Date of Electronic Publication: 2015 Sep 10. - Publication Year :
- 2015
-
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.
- Subjects :
- Animals
Carcinoma, Non-Small-Cell Lung blood
Carcinoma, Non-Small-Cell Lung diagnosis
Cell Count
Cell Line, Tumor
Cell Separation methods
Humans
Lung Neoplasms blood
Lung Neoplasms diagnosis
Mice
Mice, Transgenic
Prognosis
Surface Properties
Antibodies, Immobilized chemistry
Carcinoma, Non-Small-Cell Lung pathology
Dendrimers chemistry
ErbB Receptors analysis
Lung Neoplasms pathology
Neoplastic Cells, Circulating pathology
Polyamines chemistry
Subjects
Details
- Language :
- English
- ISSN :
- 1520-6882
- Volume :
- 87
- Issue :
- 19
- Database :
- MEDLINE
- Journal :
- Analytical chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 26312815
- Full Text :
- https://doi.org/10.1021/acs.analchem.5b02766