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Molecular characterization of chordoma xenografts generated from a novel primary chordoma cell source and two chordoma cell lines.
Abstract
OBJECT: Chordoma cells can generate solid-like tumors in xenograft models that express
some molecular characteristics of the parent tumor, including positivity for brachyury
and cytokeratins. However, there is a dearth of molecular markers that relate to chordoma
tumor growth, as well as the cell lines needed to advance treatment. The objective
in this study was to isolate a novel primary chordoma cell source and analyze the
characteristics of tumor growth in a mouse xenograft model for comparison with the
established U-CH1 and U-CH2b cell lines. METHODS: Primary cells from a sacral chordoma,
called "DVC-4," were cultured alongside U-CH1 and U-CH2b cells for more than 20 passages
and characterized for expression of CD24 and brachyury. While brachyury is believed
essential for driving tumor formation, CD24 is associated with healthy nucleus pulposus
cells. Each cell type was subcutaneously implanted in NOD/SCID/IL2Rγ(null) mice. The
percentage of solid tumors formed, time to maximum tumor size, and immunostaining
scores for CD24 and brachyury (intensity scores of 0-3, heterogeneity scores of 0-1)
were reported and evaluated to test differences across groups. RESULTS: The DVC-4
cells retained chordoma-like morphology in culture and exhibited CD24 and brachyury
expression profiles in vitro that were similar to those for U-CH1 and U-CH2b. Both
U-CH1 and DVC-4 cells grew tumors at rates that were faster than those for U-CH2b
cells. Gross tumor developed at nearly every site (95%) injected with U-CH1 and at
most sites (75%) injected with DVC-4. In contrast, U-CH2b cells produced grossly visible
tumors in less than 50% of injected sites. Brachyury staining was similar among tumors
derived from all 3 cell types and was intensely positive (scores of 2-3) in a majority
of tissue sections. In contrast, differences in the pattern and intensity of staining
for CD24 were noted among the 3 types of cell-derived tumors (p < 0.05, chi-square
test), with evidence of intense and uniform staining in a majority of U-CH1 tumor
sections (score of 3) and more than half of the DVC-4 tumor sections (scores of 2-3).
In contrast, a majority of sections from U-CH2b cells stained modestly for CD24 (scores
of 1-2) with a predominantly heterogeneous staining pattern. CONCLUSIONS: This is
the first report on xenografts generated from U-CH2b cells in which a low tumorigenicity
was discovered despite evidence of chordoma-like characteristics in vitro. For tumors
derived from a primary chordoma cell and U-CH1 cell line, similarly intense staining
for CD24 was observed, which may correspond to their similar potential to grow tumors.
In contrast, U-CH2b tumors stained less intensely for CD24. These results emphasize
that many markers, including CD24, may be useful in distinguishing among chordoma
cell types and their tumorigenicity in vivo.
Type
Journal articleSubject
BSA = bovine serum albuminCD24
FBS = fetal bovine serum
FITC = fluorescein isothiocyanate
IMDM = Iscove's modified Dulbecco's medium
MFI = mean fluorescence intensity
NSG = NOD/SCID/IL2Rγnull
PBS = phosphate-buffered saline
PCR = polymerase chain reaction
U-CH1
U-CH2b
brachyury
chordoma
oncology
xenograft
Aged
Animals
Antigens, CD24
Biomarkers, Tumor
Cell Line, Tumor
Chordoma
Disease Models, Animal
Fetal Proteins
Flow Cytometry
Heterografts
Humans
Immunohistochemistry
Keratins
Male
Mice
Polymerase Chain Reaction
Sacrum
T-Box Domain Proteins
Tumor Cells, Cultured
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https://hdl.handle.net/10161/8887Published Version (Please cite this version)
10.3171/2014.4.SPINE13262Publication Info
Karikari, Isaac O; Gilchrist, Christopher L; Jing, Liufang; Alcorta, David A; Chen,
Jun; Richardson, William J; ... Setton, Lori A (2014). Molecular characterization of chordoma xenografts generated from a novel primary chordoma
cell source and two chordoma cell lines. J Neurosurg Spine, 21(3). pp. 386-393. 10.3171/2014.4.SPINE13262. Retrieved from https://hdl.handle.net/10161/8887.This is constructed from limited available data and may be imprecise. To cite this
article, please review & use the official citation provided by the journal.
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Show full item recordScholars@Duke
Carlos Antonio Bagley
Associate Professor of Surgery
Clinical and research interests include the surgical treatment of spinal column and
spinal cord tumors, complex spinal reconstructions, as well as minimally invasive
spine techniques. Spinal oncology interests include the treatment of chordomas, spinal
cord astrocytomas and ependymomas, and spinal column metastases. In addition, laboratory
research efforts are directed at developing new techniques for the treatment of cancers
that affect the spinal cord and spinal column.
This author no longer has a Scholars@Duke profile, so the information shown here reflects
their Duke status at the time this item was deposited.
Jun Chen
Associate Professor of Orthopaedic Surgery
This author no longer has a Scholars@Duke profile, so the information shown here reflects
their Duke status at the time this item was deposited.
Mostafa Gabr
Research Associate, Senior
Dr. Gabr's research has specifically focused on the following broad areas: (i) animal
model of myelopathy, (ii) participating in clinical trials in spine field.In the last
few years, this research agenda has expanded to include collaborative projects and
publications. Dr. Gabr and his colleagues explore benefit of cervical collar following
spine fusion, spinal cord injury model, and transforaminal lumbar interbody fusion.Dr.
Gabr is the author of "Interleukin-17 synergizes with IFNI&
Isaac Obiri Karikari
Associate Professor of Neurosurgery
Michael John Kelley
Professor of Medicine
1. A major theme throughout my career has been the biology of and improving outcomes
for patients with lung cancer. Early publications examined the relationship between
specific genetic alterations in lung cancer and clinically relevant applications including
differential drug sensitivity, differentiation of metastases from second primary cancers,
and application of patient-specific mutations as epitopes for immunotherapy. Correlation
of alteration of p16 w
Lori A. Setton
Adjunct Professor of Biomedical Engineering
Research in Setton's laboratory is focused on the role of mechanical factors in the
degeneration and repair of soft tissues of the musculoskeletal system, including the
intervertebral disc, articular cartilage and meniscus. Work in the Laboratory is focused
on engineering and evaluating materials for tissue regeneration and drug delivery.
Studies combining engineering and biology are also used to determine the role of mechanical
factors to promote and control healing of cartilaginous tissues. Re
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