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Published on: May 1, 2015
Establishment and characterization of a primary human chordoma xenograft model
I-Mei Siu1, Vafi Salmasi, Brent A Orr
1Department of Neurosurgery, The Johns Hopkins University, Baltimore, MD, USA.
Object:
Chordomas are rare tumors arising from remnants of the notochord. Because of the challenges in achieving a complete resection, the radioresistant nature of these tumors, and the lack of effective chemotherapeutics, the median survival for patients with chordomas is approximately 6 years. Reproducible preclinical model systems that closely mimic the original patient's tumor are essential for the development and evaluation of effective therapeutics. Currently, there are only a few established chordoma cell lines and no primary xenograft model. In this study, the authors aimed to develop a primary chordoma xenograft model.
Methods:
The authors implanted independent tumor samples from 2 patients into athymic nude mice. The resulting xenograft line was characterized by histopathological analysis and immunohistochemical staining. The patient's tumor and serial passages of the xenograft were genomically analyzed using a 660,000 single-nucleotide polymorphism array.
Results:
A serially transplantable xenograft was established from one of the 2 patient samples. Histopathological analysis and immunohistochemical staining for S100 protein, epithelial membrane antigen, and cytokeratin AE1/AE3 of the primary patient sample and the xenografts confirmed that the xenografts were identical to the original chordoma obtained from the patient. Immunohistochemical staining and western blot analysis confirmed the presence of brachyury, a recently described marker of chordomas, in the tumor from the patient and each of the xenografts. Genome-wide variation was assessed between the patient's tumor and the xenografts and was found to be more than 99.9% concordant.
Conclusions:
To the best of their knowledge, the authors have established the first primary chordoma xenograft that will provide a useful preclinical model for this disease and a platform for therapeutic development.
Insights
Researchers developed the first primary chordoma xenograft model. This breakthrough provides a vital preclinical tool for studying chordoma (a rare bone cancer) and advancing new therapeutic strategies.
Area of Science:
- Oncology
- Cancer Biology
- Preclinical Models
Background:
- Chordomas are rare, radioresistant tumors with poor prognosis due to challenges in resection and limited treatment options.
- Existing preclinical models for chordoma are insufficient for effective therapeutic development.
- There is a critical need for reproducible models that accurately represent patient tumors.
Purpose of the Study:
- To establish a novel primary chordoma xenograft model.
- To create a reliable preclinical platform for chordoma research and drug discovery.
Main Methods:
- Tumor samples from two chordoma patients were implanted into athymic nude mice.
- Xenografts were characterized using histopathological analysis and immunohistochemical staining.
- Genomic analysis via SNP array compared patient tumors and xenografts.
Main Results:
- A serially transplantable chordoma xenograft was successfully established from one patient sample.
- Histopathology and immunohistochemistry confirmed xenografts accurately mirrored the original patient tumor.
- Over 99.9% genomic concordance was observed between patient tumors and xenografts, including brachyury expression.
Conclusions:
- The study reports the establishment of the first primary chordoma xenograft model.
- This novel model serves as a valuable preclinical tool for chordoma research.
- The xenograft platform facilitates the evaluation of potential new therapeutics for chordoma.
