UM-Chor1: Establishment and Characterization of the First Validated Clival Chordoma Cell Line

J Neurosurg. 2018 Mar;128(3):701-709. doi: 10.3171/2016.10.JNS16877. Epub 2017 Apr 21.

Abstract

OBJECTIVE Chordomas are rare malignant tumors thought to arise from remnants of the notochord. They can be located anywhere along the axial skeleton but are most commonly found in the clival and sacrococcygeal regions, where the notochord regresses during fetal development. Chordomas are resistant to many current therapies, leaving surgery as the primary method of treatment. Cancer cell lines have been useful for developing new cancer treatments in a laboratory setting that can then be transferred to the clinic, but there are only 4 validated chordoma cell lines available. The objective of this work was to establish chordoma cell lines from surgical tissue in order to expand the library of lines available for laboratory research. METHODS Chordoma tissue from the clivus was processed and sorted by flow cytometry to obtain an isolated population of chordoma cells. These cells were grown in culture and expanded until enough doublings to consider the line established. Identification of a chordoma cell line was made with known markers for chordoma, and the line was observed for ALDH (aldehyde dehydrogenase) subpopulations and tested in serum-free growth conditions as well as in vivo. RESULTS A fifth chordoma cell line, UM-Chor1, was successfully established. This is the first chordoma cell line originating from the clivus. Validation was confirmed by phenotype and positivity for the chordoma markers CD24 and brachyury. The authors also attempted to identify an ALDHhigh cell population in UM-Chor1, UCH1, and UCH2 but did not detect a distinct population. UM-Chor1 cells were able to form spheroids in serum-free culture, were successfully transduced with luciferase, and could be injected parasacrally and grown in NOD/SCID mice. CONCLUSIONS The availability of this novel clival chordoma cell line for in vitro and in vivo research provides an opportunity for developments in treatment against the disease.

Keywords: ALDH = aldehyde dehydrogenase; DAPI = 4′,6-diamidino-2-phenylindole; DEAB = diethylaminobenzaldehyde; EMA = epithelial membrane antigen; FITC = fluorescein isothiocyanate; FSP = fibroblast surface protein; GFP = green fluorescent protein; HBSS = Hank's balanced salt solution; NCAM = neural cell adhesion molecule; PBS = phosphate-buffered saline; PE = phycoerythrin; cell line; chordoma; clivus; oncology; rHIV = recombinant human immunodeficiency virus.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cell Line, Tumor*
  • Chordoma / pathology*
  • Cranial Fossa, Posterior / pathology*
  • Humans
  • Mice
  • Mice, Inbred NOD
  • Mice, SCID
  • Skull Base Neoplasms / pathology*