Modulation of phenotype and induction of irregular vessels accompany high tumorigenic potential of clonal human glioma cells xenografted to nude-rat brain

Three phenotypically different clonal human glioma cell lines were injected stereotactically into nude-rat brains, to determine their individual growt h potential and to establish an in vivo system in which different therapeut ic modalities could be tested. As assessed by serial sectioning, microscopi c evaluation, and computer analysis, the mean approximate tumour volume aft er 3-7 weeks in vivo was 0.42 mm(3) for U-343 MG, 2.6 mm(3) for U-343 MGa C 12:6, and 50.3 mm(3) for U-343 MGa 31L. When compared with the initial inje cted cell volume, only U-343 MGa 31L had increased in size, U-343 MGa C12:6 remained approximately the same but showed a certain proliferative potenti al, and U-343 MG regressed. Thus, only U-343 MGa 31L cells had high tumorig enic potential, invaded and replaced brain tissue in every direction, while U-343 MGa C12:6 cells grew in sheet-like tumour extensions along white-mat ter nerve-fibre tracts, in this respect mimicking foetal astrocytes. The tu morigenic potential of the U-343 MGa 31L cell clone was associated with a v ariable phenotype, as observed when the in vivo and in vitro characteristic s were compared. The in vivo phenotype was characterized by the loss of GFA P immunoreactivity, the gain of heterogeneously distributed cellular tenasc in, fibronectin, and laminin, but absence of extracellularly deposited mate rial, and by the formation of irregular vessels. It appears that the intrin sic capacity of glioma cells to adapt to in vivo conditions is decisive for their tumorigenicity in the brain, rather than any single phenotypic prope rty in itself. Moreover, the 2 glioma cell clones best suited for in vitro growth were no longer tumorigenic. (C) 2000 Wiley-Liss, Inc.