Abstract 4305: 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.

Estimation of Tumor Volumes by 11C-MeAIB and 18F-FDG PET in an Orthotopic Glioblastoma Rat Model

“…We used a human GBM orthotopic xenograft model. Rats (n 5 15) were implanted with 2 phenotypically different GBM cell lines: the commercially available and widely used U87MG (n 5 8) cell line, which lacks the invasive phenotype seen in human GBMs (7), and a highly invasive GBM cell line from our own laboratory, annotated T87 (n 5 7). U87MG cells were cultured as adherent cells in serum-containing medium (8), and T87 cells, as free-floating spheroids in serum-free medium (8).…”

In Vitro Modeling of Tissue-Specific 3D Microenvironments and Possibile Application to Pediatric Cancer Research

“…One of the earlier research studies on 3D culture of brain tumor cells was presented in 1977 by Carllson [223]. He studied the mitotic activity of glioma cells embedded in an agarose gel, in relation to the position of the cells in the colony, finding that the fraction of cells that incorporated tritiated thymidine decreased nearly exponentially with the depth in the colonies [223].…”

“…He studied the mitotic activity of glioma cells embedded in an agarose gel, in relation to the position of the cells in the colony, finding that the fraction of cells that incorporated tritiated thymidine decreased nearly exponentially with the depth in the colonies [223]. Over time, it has become increasingly clear that matrices in which cells are embedded is not simply a scaffold to hold them on, but a it is communicating structure important in determining cell function and behaviour [224].…”

A PRDX1‐p38α heterodimer amplifies MET‐driven invasion of IDH‐wildtype and IDH‐mutant gliomas

“…Cytodex 3 microcarriers (GE Healthcare, Uppsala, Sweden) were mixed with 10 6 glioma cells in warm culture medium and incubated for 4 hr at 37°C with 5% (v/v) CO 2 overnight. Mouse brains were prepared as described previously . Single coated beads were implanted into subcortical areas.…”