Glioblastoma multiforme (GBM): a comparative histological analysis of gliomas in mice, rats, dogs and humans
Authors: Marianela Candolfi, James Curtin, Gwendalyn D. King, Elizabeth Pluhar, Elizabeth McNiel, John R. Ohlfest, Andrew B. Freese, Peter F. Moore, Stephen W. Nichols, Pedro R. Lowenstein, Maria G. Castro
Journal: Cancer Research (2006)

2733  Although rodent glioma models have been used in preclinical glioma research for >30 years, their use remains controversial and they have been criticized for not recapitulating main pathological features of human GBMs. To address this issue, we compared experimental gliomas in mice and rats, with spontaneous GBMs in dogs, and human patients. The syngeneic mouse GL26 glioma model (20,000 GL26 cells implanted intracranially in C57Bl/6 mice) had a median survival of 25-35 days. The syngeneic rat model (5,000 CNS-1 cells implanted intracranially in to Lewis rats) had a median survival of 15-21 days. Spontaneous dog glioma samples were obtained from the Veterinary Clinic at the University of Minnesota, and human glioma samples were obtained from the Pathology Department at CMSC. General pathological appearance was studied on 5-10μm thick paraffin sections. Immunocytochemistry was used to demonstrate expression of astrocyte markers, GFAP and vimentin; blood vessel endothelial cells, Von Willebrand factor (VWF); macrophages and T cells were detected using species-specific CD3 antibodies. Gliomas in all species confirmed areas of necrosis, hemorrhage, neovascularization, cellular pleomorphism and nuclear atypia, vimentin immunoreactivity, and infiltration of T cells and macrophages. Species-specific differences were noted in the formation of pseudopalisades and tumor invasion. Human gliomas diffusely infiltrated surrounding normal brain tissue. A similar pattern was observed in dog glioma, in which the tumor border was diffuse. In the rat and mouse gliomas tumor borders were distinct, although clusters and individual tumoral cells were observed beyond the tumor margins, amongst normal brain tissue. Dog and human gliomas demonstrated typical pseudopalisades. Although the rat and mouse gliomas did not exhibit typical pseudopalisading, extensive necrotic patches were surrounded by a crown of glial cells. Our data thus indicate that CNS-1 and GL26 experimental murine gliomas share most characteristic histological features with human gliomas, even distinctive structures resembling pseudopalisades, and images suggestive of tumor infiltration of surrounding normal brain tissue. In conclusion, murine models reproduce human gliomas to a greater degree than hitherto recognized, and thus, constitute acceptable experimental models for the initial testing of novel therapies. On the other hand, spontaneous gliomas in dogs will, in addition to reproducing all typical human GBM characteristics, also allow us to model the fate of novel experimental therapies within the context of a natural disease, and a large brain. Supported by; The NIH/NINDS 1R01 NS44556.01; NIDDK 1 RO3 TW006273-01 to M.G.C.; NIH/NINDS 1 RO1 NS 42893.01, U54 NS045309-01, and 1R21 NS047298-01 to P.R.L.; NCI K08 CA89530; NCI R03 CA101030; The Linda Tallen & David Paul Kane Fellowship and the Board of Governors at CSMC.