10.1021/acs.analchem.5b02766.s001
Ja Hye Myung
Ja Hye
Myung
Monic Roengvoraphoj
Monic
Roengvoraphoj
Kevin A. Tam
Kevin A.
Tam
Tian Ma
Tian
Ma
Vincent A. Memoli
Vincent A.
Memoli
Ethan Dmitrovsky
Ethan
Dmitrovsky
Sarah J. Freemantle
Sarah J.
Freemantle
Seungpyo Hong
Seungpyo
Hong
Effective Capture of Circulating Tumor Cells from
a Transgenic Mouse Lung Cancer Model Using Dendrimer Surfaces Immobilized
with Anti-EGFR
American Chemical Society
2015
Dendrimer Surfaces Immobilized
vivo lung tumor model
vivo evaluation study
murine lung cancer cell lines
CEO
NSCLC patients overexpress epidermal growth factor receptor
ED
tumor cells
Transgenic Mouse Lung Cancer Model
CTC
Circulating Tumor Cells
LNA
nonsmall cell lung cancer
monitoring treatment responses
EGFR
surface
PAMAM
lung cancer
2015-10-06 00:00:00
Journal contribution
https://acs.figshare.com/articles/journal_contribution/Effective_Capture_of_Circulating_Tumor_Cells_from_a_Transgenic_Mouse_Lung_Cancer_Model_Using_Dendrimer_Surfaces_Immobilized_with_Anti_EGFR/2125132
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, <i>p</i> < 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
(<i>p</i> < 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.