title: Invasion of primary glioma- and cell line-derived spheroids implanted into corticostriatal slice cultures.
abstract: Gliomas are highly invasive tumors and the pronounced invasive features of gliomas prevent radical surgical resection. In the search for new therapeutics targeting invasive glioma cells, in vivo-like in vitro models are of great interest. We developed and evaluated an in vivo-like in vitro model preserving the invasive features and stem cell features of glioma cells. Fluorescently labelled primary glioma spheroids and U87MG cell line-derived spheroids were implanted into organotypic rat corticostriatal slice cultures and the invasion was followed over time by confocal microscopy. The invasion was validated immunohistochemically with paraffin sections using a human-specific vimentin antibody. Moreover, the preservation of immature stem cell features was evaluated immunohistochemically using the stem cell markers CD133, Sox2, Bmi-1 and nestin. The confocal and immunohistochemical results showed that the primary glioma spheroid area was constant or decreasing after implantation, with a clear increase in the number of invading cells over time. In contrast, the U87MG spheroid area increased after implantation, with no convincing tumor cell invasion. High levels of Bmi-1 and nestin were found in all spheroids, whereas high levels of Sox2 and low to moderate levels of CD133 were only found in the primary spheroids. In conclusion, the invasion of gliomas is preserved using primary glioma spheroids. Some stem cell features are preserved as well, making this model useful in drug development elucidating both invasion and cancer stemness at the early in vitro level.
authors.affiliation: Department of Pathology, Odense University Hospital, Odense, Denmark.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Aaberg-Jessen
authors.forename: Annette
authors.initials: A
authors.lastname: Nørregaard
authors.forename: Karina
authors.initials: K
authors.lastname: Christensen
authors.forename: Christian B
authors.initials: CB
authors.lastname: Pedersen
authors.forename: Claus
authors.initials: C
authors.lastname: Andersen
authors.forename: Bjarne W
authors.initials: BW
authors.lastname: Kristensen
mesh_terms: D000071916:AC133 Antigen; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D001254:Astrocytoma / Q000378:metabolism / Q000473:pathology*; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D001932:Brain Neoplasms / Q000378:metabolism / Q000473:pathology*; D002465:Cell Movement / Q000502:physiology*; D018920:Coculture Techniques; D004195:Disease Models, Animal; D005910:Glioma / Q000378:metabolism / Q000473:pathology*; D006023:Glycoproteins / Q000378:metabolism; D006801:Humans; D007381:Intermediate Filament Proteins / Q000378:metabolism; D018613:Microscopy, Confocal; D009419:Nerve Tissue Proteins / Q000378:metabolism; D064231:Nestin; D010455:Peptides / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D055748:SOXB1 Transcription Factors / Q000378:metabolism; D018874:Spheroids, Cellular / Q000378:metabolism / Q000473:pathology*; D046509:Tissue Culture Techniques
chemical_list: D000071916:AC133 Antigen; D015703:Antigens, CD; D006023:Glycoproteins; D007381:Intermediate Filament Proteins; C577484:NES protein, human; D009419:Nerve Tissue Proteins; C577486:Nes protein, rat; D064231:Nestin; C000606023:PROM1 protein, human; D010455:Peptides; C000606025:Prom1 protein, rat; D011518:Proto-Oncogene Proteins; D055748:SOXB1 Transcription Factors
keywords: Glioma; invasion; organotypic slice cultures; spheroids