UM-Chor1: establishment and characterization of the first validated clival chordoma cell line.

John Henry Owen, Christine M Komarck, Anthony C Wang, Waleed M Abuzeid, Richard F Keep, Erin L McKean, Stephen Sullivan, Xing Fan, Mark E P Prince
Author Information
  1. John Henry Owen: Departments of1Otolaryngology-Head and Neck Surgery.
  2. Christine M Komarck: Departments of1Otolaryngology-Head and Neck Surgery.
  3. Anthony C Wang: 2Neurosurgery, and.
  4. Waleed M Abuzeid: Departments of1Otolaryngology-Head and Neck Surgery.
  5. Richard F Keep: 2Neurosurgery, and.
  6. Erin L McKean: Departments of1Otolaryngology-Head and Neck Surgery.
  7. Stephen Sullivan: 2Neurosurgery, and.
  8. Xing Fan: 2Neurosurgery, and.
  9. Mark E P Prince: Departments of1Otolaryngology-Head and Neck Surgery.

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 ALDH 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

References

  1. Clin Transl Med. 2013 Jan 17;2(1):3 [PMID: 23369605]
  2. Arch Pathol Lab Med. 2010 Aug;134(8):1181-7 [PMID: 20670140]
  3. J Exp Clin Cancer Res. 2014 Dec 14;33:105 [PMID: 25499255]
  4. Int J Oncol. 2012 Feb;40(2):443-51 [PMID: 22002331]
  5. Neuro Oncol. 2014 Jan;16(1):72-80 [PMID: 24366975]
  6. Int J Med Sci. 2013 Oct 31;10(13):1805-16 [PMID: 24324357]
  7. Biochem Biophys Res Commun. 2005 Dec 30;338(4):1890-6 [PMID: 16288985]
  8. Int J Radiat Oncol Biol Phys. 2006 Aug 1;65(5):1514-21 [PMID: 16757128]
  9. J Neurosurg. 2012 Apr;116(4):810-20 [PMID: 22283189]
  10. Expert Rev Gastroenterol Hepatol. 2008 Feb;2(1):125-33 [PMID: 19072375]
  11. Histol Histopathol. 2009 Mar;24(3):309-16 [PMID: 19130400]
  12. J Neuropathol Exp Neurol. 2016 Feb;75(2):111-20 [PMID: 26733585]
  13. PLoS One. 2013 Nov 06;8(11):e79950 [PMID: 24223206]
  14. J Clin Pathol. 2001 Dec;54(12):945-50 [PMID: 11729215]
  15. Dis Markers. 2014;2014:514753 [PMID: 24591762]
  16. Cancer Res. 2011 Feb 1;71(3):895-905 [PMID: 21266361]
  17. Ann Surg Oncol. 2009 Feb;16(2):506-14 [PMID: 19050962]
  18. Appl Immunohistochem Mol Morphol. 2009 Mar;17(2):131-8 [PMID: 19521276]
  19. Mod Pathol. 2008 Dec;21(12):1461-9 [PMID: 18820665]
  20. Oncol Rep. 2009 Nov;22(5):1149-56 [PMID: 19787233]
  21. Cell Mol Immunol. 2010 Mar;7(2):100-3 [PMID: 20154703]
  22. Cancer. 2000 May 1;88(9):2122-34 [PMID: 10813725]
  23. Sarcoma. 2010;2010:630129 [PMID: 21253487]
  24. J Neurosurg. 2014 Feb;120(2):331-6 [PMID: 24286145]
  25. Chest. 1992 Sep;102(3):832-7 [PMID: 1516411]
  26. PLoS One. 2012;7(8):e43664 [PMID: 22928012]
  27. Nat Genet. 2009 Nov;41(11):1176-8 [PMID: 19801981]
  28. Cell Stem Cell. 2007 Nov;1(5):555-67 [PMID: 18371393]
  29. Head Neck. 2016 Apr;38 Suppl 1:E459-67 [PMID: 25677579]
  30. Radiat Oncol. 2011 Sep 14;6:116 [PMID: 21914223]
  31. Nanomedicine (Lond). 2012 Apr;7(4):597-615 [PMID: 22471722]
  32. Pathol Oncol Res. 2009 Jun;15(2):279-83 [PMID: 18752058]
  33. J Neurosurg. 2011 Oct;115(4):760-9 [PMID: 21699479]
  34. Hum Genet. 2014 Oct;133(10):1289-97 [PMID: 24990759]
  35. Head Neck. 2010 Sep;32(9):1195-201 [PMID: 20073073]
  36. J Pathol. 2011 Feb;223(3):327-35 [PMID: 21171078]
  37. Oncologist. 2007 Nov;12(11):1344-50 [PMID: 18055855]
  38. CA Cancer J Clin. 2007 Jan-Feb;57(1):43-66 [PMID: 17237035]
  39. Biochimie. 2003 Jun;85(6):565-73 [PMID: 12829373]
  40. BMC Cancer. 2010 Jan 28;10:22 [PMID: 20109225]

Grants

  1. F32 NS074744/NINDS NIH HHS
  2. R01 CA148621/NCI NIH HHS
  3. R01 CA163737/NCI NIH HHS

MeSH Term

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

Word Cloud

Created with Highcharts 10.0.0=cellchordomalinelinesclivalclivuspopulationcellsALDHUM-Chor1Chordomasnotochordcantreatmentlaboratoryvalidatedavailabletissueresearchgrowncultureestablishedmarkersaldehydedehydrogenaseserum-freevivosuccessfullyfirstproteinOBJECTIVEraremalignanttumorsthoughtariseremnantslocatedanywherealongaxialskeletoncommonlyfoundsacrococcygealregionsregressesfetaldevelopmentresistantmanycurrenttherapiesleavingsurgeryprimarymethodCancerusefuldevelopingnewcancertreatmentssettingtransferredclinic4objectiveworkestablishsurgicalorderexpandlibraryMETHODSChordomaprocessedsortedflowcytometryobtainisolatedexpandedenoughdoublingsconsiderIdentificationmadeknownobservedsubpopulationstestedgrowthconditionswellRESULTSfifthoriginatingValidationconfirmedphenotypepositivityCD24brachyuryauthorsalsoattemptedidentifyUCH1UCH2detectdistinctableformspheroidstransducedluciferaseinjectedparasacrallyNOD/SCIDmiceCONCLUSIONSavailabilitynovelvitroprovidesopportunitydevelopmentsdiseaseUM-Chor1:establishmentcharacterizationDAPI4′6-diamidino-2-phenylindoleDEABdiethylaminobenzaldehydeEMAepithelialmembraneantigenFITCfluoresceinisothiocyanateFSPfibroblastsurfaceGFPgreenfluorescentHBSSHank'sbalancedsaltsolutionNCAMneuraladhesionmoleculePBSphosphate-bufferedsalinePEphycoerythrinoncologyrHIVrecombinanthumanimmunodeficiencyvirus

Similar Articles

Cited By