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Effective Capture of Circulating Tumor Cells from a Transgenic Mouse Lung Cancer Model Using Dendrimer Surfaces Immobilized with Anti-EGFR
journal contribution
posted on 2015-10-06, 00:00 authored by Ja Hye Myung, Monic Roengvoraphoj, Kevin A. Tam, Tian Ma, Vincent A. Memoli, Ethan Dmitrovsky, Sarah J. Freemantle, Seungpyo HongThe 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.
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Dendrimer Surfaces Immobilizedvivo lung tumor modelvivo evaluation studymurine lung cancer cell linesCEONSCLC patients overexpress epidermal growth factor receptorEDtumor cellsTransgenic Mouse Lung Cancer ModelCTCCirculating Tumor CellsLNAnonsmall cell lung cancermonitoring treatment responsesEGFRsurfacePAMAMlung cancer
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