A novel chordoma xenograft allows in vivo drug testing and reveals the importance of NF-kB signaling in chordoma biology

Matteo M. Trucco, Ola Awad, Breelyn A. Wilky, Seth D. Goldstein, Ruili Huang, Robert L. Walker, Preeti Shah, Varalakshmi Katuri, Naheed Gul, Yuelin J. Zhu, Edward F. McCarthy, Ido Paz-Priel, Paul S. Meltzer, Christopher P. Austin, Menghang Xia, David M. Loeb

Research output: Contribution to journalArticle


Chordoma is a rare primary bone malignancy that arises in the skull base, spine and sacrum and originates from remnants of the notochord. These tumors are typically resistant to conventional chemotherapy, and to date there are no FDA-approved agents to treat chordoma. The lack of in vivo models of chordoma has impeded the development of new therapies for this tumor. Primary tumor from a sacral chordoma was xenografted into NOD/SCID/IL-2R y-null mice. The xenograft is serially transplantable and was characterized by both gene expression analysis and whole genome SNP genotyping. The NIH Chemical Genomics Center performed high-throughput screening of 2,816 compounds using two established chordoma cell lines, U-CH1 and U-CH2B. The screen yielded several compounds that showed activity and two, sunitinib and bortezomib, were tested in the xenograft. Both agents slowed the growth of the xenograft tumor. Sensitivity to an inhibitor of IkB, as well as inhibition of an NF-kB gene expression signature demonstrated the importance of NF-kB signaling for chordoma growth. This serially transplantable chordoma xenograft is thus a practical model to study chordomas and perform in vivo preclinical drug testing.

Original languageEnglish (US)
Article numbere79950
JournalPloS one
Issue number11
StatePublished - Nov 6 2013


ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

Cite this

Trucco, M. M., Awad, O., Wilky, B. A., Goldstein, S. D., Huang, R., Walker, R. L., Shah, P., Katuri, V., Gul, N., Zhu, Y. J., McCarthy, E. F., Paz-Priel, I., Meltzer, P. S., Austin, C. P., Xia, M., & Loeb, D. M. (2013). A novel chordoma xenograft allows in vivo drug testing and reveals the importance of NF-kB signaling in chordoma biology. PloS one, 8(11), [e79950]. https://doi.org/10.1371/journal.pone.0079950