title: Intracranial glioblastoma models in preclinical neuro-oncology: neuropathological characterization and tumor progression.
abstract: Although rodent glioblastoma (GBM) models have been used for over 30 years, the extent to which they recapitulate the characteristics encountered in human GBMs remains controversial. We studied the histopathological features of dog GBM and human xenograft GBM models in immune-deficient mice (U251 and U87 GBM in nude Balb/c), and syngeneic GBMs in immune-competent rodents (GL26 cells in C57BL/6 mice, CNS-1 cells in Lewis rats). All GBMs studied exhibited neovascularization, pleomorphism, vimentin immunoreactivity, and infiltration of T-cells and macrophages. All the tumors showed necrosis and hemorrhages, except the U87 human xenograft, in which the most salient feature was its profuse neovascularization. The tumors differed in the expression of astrocytic intermediate filaments: human and dog GBMs, as well as U251 xenografts expressed glial fibrillary acidic protein (GFAP) and vimentin, while the U87 xenograft and the syngeneic rodent GBMs were GFAP(-) and vimentin(+). Also, only dog GBMs exhibited endothelial proliferation, a key feature that was absent in the murine models. In all spontaneous and implanted GBMs we found histopathological features compatible with tumor invasion into the non-neoplastic brain parenchyma. Our data indicate that murine models of GBM appear to recapitulate several of the human GBM histopathological features and, considering their reproducibility and availability, they constitute a valuable in vivo system for preclinical studies. Importantly, our results indicate that dog GBM emerges as an attractive animal model for testing novel therapies in a spontaneous tumor in the context of a larger brain.
authors.affiliation: Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, UCLA, Los Angeles, CA, USA.
authors.forename: Marianela
authors.initials: M
authors.lastname: Candolfi
authors.forename: James F
authors.initials: JF
authors.lastname: Curtin
authors.forename: W Stephen
authors.initials: WS
authors.lastname: Nichols
authors.forename: Akm G
authors.initials: AG
authors.lastname: Muhammad
authors.forename: Gwendalyn D
authors.initials: GD
authors.lastname: King
authors.forename: G Elizabeth
authors.initials: GE
authors.lastname: Pluhar
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: McNiel
authors.forename: John R
authors.initials: JR
authors.lastname: Ohlfest
authors.forename: Andrew B
authors.initials: AB
authors.lastname: Freese
authors.forename: Peter F
authors.initials: PF
authors.lastname: Moore
authors.forename: Jonathan
authors.initials: J
authors.lastname: Lerner
authors.forename: Pedro R
authors.initials: PR
authors.lastname: Lowenstein
authors.forename: Maria G
authors.initials: MG
authors.lastname: Castro
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000662:veterinary; D004195:Disease Models, Animal; D018450:Disease Progression; D004283:Dog Diseases / Q000473:pathology*; D004285:Dogs; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D005909:Glioblastoma / Q000378:metabolism / Q000473:pathology* / Q000662:veterinary; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D051381:Rats; D011917:Rats, Inbred Lew; D014746:Vimentin / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays / Q000379:methods*
chemical_list: D005904:Glial Fibrillary Acidic Protein; D014746:Vimentin