Invasiveness in primary intracranial tumors: Part 1. An experimental model using cloned SV40 virus-produced hamster brain tumors.

This report presents an experimental model for study of the cellular and molecular biology of invasiveness in tumors. It uses SV40 virus for the production of primary intracranial tumors that are invasive for normal brain and vary markedly and predictably in this invasiveness. Cell cultures of dissociated 1- to 2-day-old Syrian hamster cerebral cortex (Cx), brain stem (Bs), cerebellar hemisphere (Cbh), and cerebellar vermis (Cbv) were transformed with SV40 virus and inoculated intracerebrally into newborn hamsters. All 368 animals that developed intracranial tumors were killed, and tumor was taken for histological and immunofluorescence studies, assessment of extent of invasiveness, and preparation of cell cultures from which cells were cloned by dilution plating or growth in soft agar. A few hamsters were perfused with glutaraldehyde for studies of tumor ultrastructure. All cloned and uncloned tumor cells were reinoculated to produce second- and third-passage tumors. Characteristic differences in morphology and growth rate were observed between normal astrocytes derived from each brain region, and these phenotypic differences were retained after virus transformation and tumor production. Cloned and uncloned Cx cell-derived tumors of second and third passage diffusely invaded adjacent normal brain, although those of first passage invaded only slightly. Except for extracerebral spread, these tumors resembled human astrocytic series tumors. Bs and some Cbh cell-derived tumors were also astrocytic but more undifferentiated and only slightly invasive; Cbv and other Cbh cell-derived tumors were sarcomatous and only extended along perivascular spaces or were not invasive at all. The tumor cells contained glial fibrillary acidic protein and SV40 T-antigen. These results suggest that astrocytes from different brain regions vary in genomic stability and support the theory that differences in invasiveness reflect the development of heterogeneity and subsequent selection of more aggressive subpopulations of cells.