title: Development of patient-derived xenograft models from a spontaneously immortal low-grade meningioma cell line, KCI-MENG1.
abstract: BACKGROUND
  There is a paucity of effective therapies for recurrent/aggressive meningiomas. Establishment of improved in vitro and in vivo meningioma models will facilitate development and testing of novel therapeutic approaches.
  
  
  METHODS
  A primary meningioma cell line was generated from a patient with an olfactory groove meningioma. The cell line was extensively characterized by performing analysis of growth kinetics, immunocytochemistry, telomerase activity, karyotype, and comparative genomic hybridization. Xenograft models using immunocompromised SCID mice were also developed.
  
  
  RESULTS
  Histopathology of the patient tumor was consistent with a WHO grade I typical meningioma composed of meningothelial cells, whorls, and occasional psammoma bodies. The original tumor and the early passage primary cells shared the standard immunohistochemical profile consistent with low-grade, good prognosis meningioma. Low passage KCI-MENG1 cells were composed of two cell types with spindle and round morphologies, showed linear growth curve, had very low telomerase activity, and were composed of two distinct unrelated clones on cytogenetic analysis. In contrast, high passage cells were homogeneously round, rapidly growing, had high telomerase activity, and were composed of a single clone with a near triploid karyotype containing 64-66 chromosomes with numerous aberrations. Following subcutaneous and orthotopic transplantation of low passage cells into SCID mice, firm tumors positive for vimentin and progesterone receptor (PR) formed, while subcutaneous implant of high passage cells yielded vimentin-positive, PR-negative tumors, concordant with a high-grade meningioma.
  
  
  CONCLUSIONS
  Although derived from a benign meningioma specimen, the newly-established spontaneously immortal KCI-MENG1 meningioma cell line can be utilized to generate xenograft tumor models with either low- or high-grade features, dependent on the cell passage number (likely due to the relative abundance of the round, near-triploid cells). These human meningioma mouse xenograft models will provide biologically relevant platforms from which to investigate differences in low- vs. high-grade meningioma tumor biology and disease progression as well as to develop novel therapies to improve treatment options for poor prognosis or recurrent meningiomas.
authors.affiliation: Department of Neurosurgery, Wayne State University, 4160 John R Street, Suite 930, Detroit, MI, 48201, USA. smichelh@med.wayne.edu.
authors.forename: Sharon K
authors.initials: SK
authors.lastname: Michelhaugh
authors.affiliation: Department of Neurosurgery, Wayne State University, 4160 John R Street, Suite 930, Detroit, MI, 48201, USA. aguastel@med.wayne.edu.|Department of Oncology, Wayne State University, Detroit, MI, 48201, USA. aguastel@med.wayne.edu.
authors.forename: Anthony R
authors.initials: AR
authors.lastname: Guastella
authors.affiliation: Department of Neurosurgery, Wayne State University, 4160 John R Street, Suite 930, Detroit, MI, 48201, USA. kaushik.varadarajan@wayne.edu.
authors.forename: Kaushik
authors.initials: K
authors.lastname: Varadarajan
authors.affiliation: Department of Neurosurgery, Wayne State University, 4160 John R Street, Suite 930, Detroit, MI, 48201, USA. nklinger@med.wayne.edu.
authors.forename: Neil V
authors.initials: NV
authors.lastname: Klinger
authors.affiliation: Department of Neurosurgery, Wayne State University, 4160 John R Street, Suite 930, Detroit, MI, 48201, USA. pparajuli@med.wayne.edu.|Karmanos Cancer Institute, Detroit, MI, 48201, USA. pparajuli@med.wayne.edu.
authors.forename: Prahlad
authors.initials: P
authors.lastname: Parajuli
authors.affiliation: Department of Pathology, Wayne State University, Detroit, MI, 48201, USA. ahmada@karmanos.org.|Karmanos Cancer Institute, Detroit, MI, 48201, USA. ahmada@karmanos.org.
authors.forename: Aamir
authors.initials: A
authors.lastname: Ahmad
authors.affiliation: Department of Pathology, Wayne State University, Detroit, MI, 48201, USA. sseth@med.wayne.edu.
authors.forename: Seema
authors.initials: S
authors.lastname: Sethi
authors.affiliation: Department of Oncology, Wayne State University, Detroit, MI, 48201, USA. kameelo@karmanos.org.|Karmanos Cancer Institute, Detroit, MI, 48201, USA. kameelo@karmanos.org.
authors.forename: Amro
authors.initials: A
authors.lastname: Aboukameel
authors.affiliation: Department of Neurosurgery, Wayne State University, 4160 John R Street, Suite 930, Detroit, MI, 48201, USA. skiousis@med.wayne.edu.
authors.forename: Sam
authors.initials: S
authors.lastname: Kiousis
authors.affiliation: Department of Neurosurgery, Wayne State University, 4160 John R Street, Suite 930, Detroit, MI, 48201, USA. izitron@gmail.com.
authors.forename: Ian M
authors.initials: IM
authors.lastname: Zitron
authors.affiliation: Department of Pathology, Wayne State University, Detroit, MI, 48201, USA. sebrahim@med.wayne.edu.
authors.forename: Salah A
authors.initials: SA
authors.lastname: Ebrahim
authors.affiliation: Department of Oncology, Wayne State University, Detroit, MI, 48201, USA. polinl@karmanos.org.|Karmanos Cancer Institute, Detroit, MI, 48201, USA. polinl@karmanos.org.
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Polin
authors.affiliation: Department of Pathology, Wayne State University, Detroit, MI, 48201, USA. fsarkar@med.wayne.edu.|Karmanos Cancer Institute, Detroit, MI, 48201, USA. fsarkar@med.wayne.edu.
authors.forename: Fazlul H
authors.initials: FH
authors.lastname: Sarkar
authors.affiliation: Department of Oncology, Wayne State University, Detroit, MI, 48201, USA. bollig@karmanos.org.|Karmanos Cancer Institute, Detroit, MI, 48201, USA. bollig@karmanos.org.
authors.forename: Aliccia
authors.initials: A
authors.lastname: Bollig-Fischer
authors.affiliation: Department of Neurosurgery, Wayne State University, 4160 John R Street, Suite 930, Detroit, MI, 48201, USA. smittal@med.wayne.edu.|Department of Oncology, Wayne State University, Detroit, MI, 48201, USA. smittal@med.wayne.edu.|Karmanos Cancer Institute, Detroit, MI, 48201, USA. smittal@med.wayne.edu.
authors.forename: Sandeep
authors.initials: S
authors.lastname: Mittal
mesh_terms: D000818:Animals; D063646:Carcinogenesis / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D048430:Cell Shape; D002871:Chromosome Banding; D055028:Comparative Genomic Hybridization; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007621:Karyotyping; D008577:Meningeal Neoplasms / Q000473:pathology*; D008579:Meningioma / Q000473:pathology*; D016513:Mice, SCID; D008875:Middle Aged; D060787:Neoplasm Grading; D059906:Neuroimaging; D023041:Xenograft Model Antitumor Assays