Molecular characterization of chordoma xenografts generated from a novel primary chordoma cell source and two chordoma cell lines.
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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.
SubjectBSA = bovine serum albumin
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
Cell Line, Tumor
Disease Models, Animal
Polymerase Chain Reaction
T-Box Domain Proteins
Tumor Cells, Cultured
Published Version (Please cite this version)10.3171/2014.4.SPINE13262
Publication InfoAlcorta, DA; Bagley, CA; Bell, RD; Chen, J; Gabr, Mostafa A; Gilchrist, CL; ... 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 http://hdl.handle.net/10161/8887.
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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.
Professor of Orthopaedic Surgery
1. Current research includes investigation of biomechanical aspects of cervical injury with head impact. This involves cadaveric work with high-speed photography and load cells to ascertain the mechanism for spinal fractures. 2. An animal model is being used to evaluate the biomechanics of cervical laminectomy versus laminoplasty compared to the normal spine. A portion of the animals are developing myelopathy secondary to instability after the surgical procedure and this is bei
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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