title: Tumor versus stromal cells in culture--survival of the fittest?
abstract: Two of the signature genetic events that occur in human gliomas, EGFR amplification and IDH mutation, are poorly represented in experimental models in vitro. EGFR amplification, for example, occurs in 40 to 50% of GBM, and yet, EGFR amplification is rarely preserved in cell cultures derived from human tumors. To analyze the fate of EGFR amplified and IDH mutated cells in culture, we followed the development over time of cultures derived from human xenografts in nude rats enriched for tumor cells with EGFR amplification and of cultures derived from patient samples with IDH mutations, in serum monolayer and spheroid suspension culture, under serum and serum free conditions. We observed under serum monolayer conditions, that nestin positive or nestin and SMA double positive rat stromal cells outgrew EGFR amplified tumor cells, while serum spheroid cultures preserved tumor cells with EGFR amplification. Serum free suspension culture exhibited a more variable cell composition in that the resultant cell populations were either predominantly nestin/SOX2 co-expressing rat stromal cells or human tumor cells, or a mixture of both. The selection for nestin/SMA positive stromal cells under serum monolayer conditions was also consistently observed in human oligodendrogliomas and oligoastrocytomas with IDH mutations. Our results highlight for the first time that serum monolayer conditions can select for stromal cells instead of tumor cells in certain brain tumor subtypes. This result has an important impact on the establishment of new tumor cell cultures from brain tumors and raises the question of the proper conditions for the growth of the tumor cell populations of interest.
authors.affiliation: Department of Biomedicine, University of Bergen, Bergen, Norway.
authors.forename: Krishna M
authors.initials: KM
authors.lastname: Talasila
authors.affiliation: Department of Biomedicine, University of Bergen, Bergen, Norway.
authors.forename: Narve
authors.initials: N
authors.lastname: Brekka
authors.affiliation: Department of Pathology, Haukeland University Hospital, Bergen, Norway.
authors.forename: Kjersti
authors.initials: K
authors.lastname: Mangseth
authors.affiliation: NorLux Neuro-Oncology Laboratory, Department of Oncology, Centre de Recherche Public de la Santé (CRP-Santé), Luxembourg, Luxembourg.
authors.forename: Daniel
authors.initials: D
authors.lastname: Stieber
authors.affiliation: Department of Biomedicine, University of Bergen, Bergen, Norway.
authors.forename: Lasse
authors.initials: L
authors.lastname: Evensen
authors.affiliation: Department of Biomedicine, University of Bergen, Bergen, Norway.
authors.forename: Gro V
authors.initials: GV
authors.lastname: Rosland
authors.affiliation: Department of Biomedicine, University of Bergen, Bergen, Norway.
authors.forename: Anja
authors.initials: A
authors.lastname: Torsvik
authors.affiliation: Department of Biomedicine, University of Bergen, Bergen, Norway.
authors.forename: Marek
authors.initials: M
authors.lastname: Wagner
authors.affiliation: NorLux Neuro-Oncology Laboratory, Department of Oncology, Centre de Recherche Public de la Santé (CRP-Santé), Luxembourg, Luxembourg.
authors.forename: Simone P
authors.initials: SP
authors.lastname: Niclou
authors.affiliation: Department of Neurosurgery, Haukeland University Hospital, Bergen, Norway.
authors.forename: Rupavathana
authors.initials: R
authors.lastname: Mahesparan
authors.affiliation: Department of Pathology, Haukeland University Hospital, Bergen, Norway.
authors.forename: Olav K
authors.initials: OK
authors.lastname: Vintermyr
authors.affiliation: Department of Biomedicine, University of Bergen, Bergen, Norway ; NorLux Neuro-Oncology Laboratory, Department of Oncology, Centre de Recherche Public de la Santé (CRP-Santé), Luxembourg, Luxembourg.
authors.forename: Rolf
authors.initials: R
authors.lastname: Bjerkvig
authors.affiliation: Department of Biomedicine, University of Bergen, Bergen, Norway.
authors.forename: Janice M
authors.initials: JM
authors.lastname: Nigro
authors.affiliation: Department of Biomedicine, University of Bergen, Bergen, Norway ; Department of Pathology, Haukeland University Hospital, Bergen, Norway.
authors.forename: Hrvoje
authors.initials: H
authors.lastname: Miletic
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000378:metabolism; D066246:ErbB Receptors / Q000378:metabolism*; D005909:Glioblastoma / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D009154:Mutation; D009837:Oligodendroglioma / Q000378:metabolism; D051381:Rats; D017154:Stromal Cells / Q000473:pathology*; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
chemical_list: D066246:ErbB Receptors