Correlation of in vitro infiltration with glioma histological type in organotypic brain slices

Abstract

Diffuse invasion of the brain, an intrinsic property of gliomas, renders these tumours incurable, and is a principal determinant of their spatial and temporal growth. Knowledge of the invasive potential of gliomas is highly desired in order to understand their behaviour in vivo. Comprehensive ex vivo invasion studies including tumours of different histological types and grades are however lacking, mostly because reliable physiological invasion assays have been difficult to establish. Using an organotypic rodent brain slice assay, we evaluated the invasiveness of 42 grade II -IV glioma biopsy specimens, and correlated it with the histological phenotype, the absence or presence of deletions on chromosomes 1p and 19q assessed by fluorescent in situ hybridisation, and proliferation and apoptosis indices assessed by immunocytochemistry. Oligodendroglial tumours with 1p/19q loss were less invasive than astrocytic tumours of similar tumour grade. Correlation analysis of invasiveness cell proliferation and apoptosis further suggested that grade II -III oligodendroglial tumours with 1p/19q loss grow in situ as relatively circumscribed compact masses in contrast to the more infiltrative and more diffuse astrocytomas. Lower invasiveness may be an important characteristic of oligodendroglial tumours, adding to our understanding of their more indolent clinical evolution and responsiveness to therapy.

Differentiation between Oligodendroglioma Genotypes Using Dynamic Susceptibility Contrast Perfusion-Weighted Imaging and Proton MR Spectroscopy

“…This argument is supported by the fact that high rCBV correlates with increased Cho levels in gliomas. 40 Histopathologic analysis shows that oligodendrogliomas with 1p/19q LOH grow as compact and hypercellular lesions, 41 corroborating our observation of elevated levels of Cho/Cr in these oligodendrogliomas. Higher proliferation of neoplastic cells and elevated metabolic rate lead to hypoxic regions; this cycle ultimately leads to energy failure and cell death that results in necrosis.…”

Glioma Dynamics and Computational Models: A Review of Segmentation, Registration, and In Silico Growth Algorithms and their Clinical Applications

“…The rules of division and invasion are the key elements of this approach. Since these models describe the tumor growth at the microscopic scale, their prediction could be also validated in clinical practice by microscopic histological analysis of tumor samples (spatial correlation in graph cells [59]) or in vitro, with dynamic study of glial cells migrations [60]. On the contrary, the partial differential equations approach does not tell anything about the spatial ordering of the tumor cells: it simulates a coarse-grained cell density.…”

Three-Dimensional In Vitro Models in Glioma Research - Focus on Spheroids

“…In the first real invasion studies, tissue aggregates from rat brain or chick heart were (LundJohansen et al, 1990) placed next to the tumor tissue, but first with the development of the organotypic brain slice culture, it was possible to preserve the brain architecture and organization in an optimal way, thereby creating the conditions necessary for a more in vivo-like model of glioma invasion. Several groups have been using this model to investigate the invasion of glioma cell into organotypic brain slice cultures Caspani et al, 2006;De et al, 2002;Eyupoglu et al, 2005;Guillamo et al, 2009;Jensen et al 2010;Matsumura et al, 2000;Ohnishi et al, 1998;Palfi et al, 2004;Stoppini et al, 1991). In one study using this model, invasion was shown to be associated with the histological type and grade of the tumor (Palfi et al, 2004) and in another study invasion and tumor-induced neurotoxicity was shown to be associated (Eyupoglu et al, 2005).…”

“…Several groups have been using this model to investigate the invasion of glioma cell into organotypic brain slice cultures Caspani et al, 2006;De et al, 2002;Eyupoglu et al, 2005;Guillamo et al, 2009;Jensen et al 2010;Matsumura et al, 2000;Ohnishi et al, 1998;Palfi et al, 2004;Stoppini et al, 1991). In one study using this model, invasion was shown to be associated with the histological type and grade of the tumor (Palfi et al, 2004) and in another study invasion and tumor-induced neurotoxicity was shown to be associated (Eyupoglu et al, 2005). Most interestingly, quantitative analysis of invasion has also been performed (De et al, 2002) using confocal laser scanning microscopy and a three-dimensional visualization after having followed invasion over several weeks (Matsumura et al, 2000).…”

“…Organotypic brain slice cultures from rodents have been used in a variety of different studies using tissue obtained from different areas in the brain. The organotypic brain slice cultures used in the invasion studies varied from explants from spinal cord (Caspani et al, 2006), brain slices cut in the sagittal plane (Caspani et al, 2006) and the coronal plane (De et al, 2002;Guillamo et al, 2009;Matsumura et al, 2000;Ohnishi et al, 1998;Palfi et al, 2004) as well as entorhinohippocampal slice cultures (Eyupoglu et al, 2005). Since glioblastomas are often located in the subcortical white matter of the cerebral hemisphere and tumor infiltration often extends into the adjacent cortex and through corpus callosum (Louis et al, 2007) we have used organotypic corticostriatal brain slice cultures with cortex, striatum and corpus callosum for our studies of the invasive features of the glioblastoma cells.…”