THE CHARACTERIZATION OF NUCLEAR-DNA CONTENT, THE PROLIFERATIVE ACTIVITY AND THE IMMUNOHISTOCHEMICAL EXPRESSION OF GFAP, VIM, LEU-7, S-100, P53 AND CATHEPSIN-D IN HUMAN GLIOBLASTOMA MULTIFORMES (HGBMS) VERSUS HUMAN GBM CELL-LINES GRAFTED INTO THE BRAINS OF NUDE-MICE

Experimental models relating to human glioblastoma multiformes (hGBMs) involve the intracranial or intracerebral injection of human GBM cell s into nude mice or rats. The aim of the present study was to compare a number of biological characteristics of hGBMs as opposed to experime ntal GBMs obtained by grafting either human U87 or U373 glioblastoma c ells into the brains of nude mice. Biological assessments involve four distinct sets of parameters, i.e. i) the determination of the nuclear DNA content, ii) the determination of proliferative activity, iii) th e assessment of p53 nuclear phosphoprotein immunohistochemical reactiv ity, and iv) the assessment of GFAP, VIM, LEU-7, S-100 and CAT D prote in immunohistochemical reactivity. While most of the human glioblastom a multiformes (hGBMs) under study were immunohistochemically reactive to GFAP, S-100, LEU-7 and VIM as indeed were the experimental U373 GBM s, the U87 ones were reactive to VIM only. Furthermore, the U87 GBMs a ppeared to be more aggressive than the U373 ones since the former were associated with a shorter tumor-bearing mouse survival time than the latter. Such aggressiveness was further associated with a proliferativ e activity and a cathepsin D immunoreactivity, both of which were mark edly higher in the U87 GBMs than in the U373 GBMs. These two experimen tal GBM models also exhibited tumors which were predominantly diploid. The present study shows that it is possible to set up experimentally in vivo models which strongly mimic human glioblastoma multiformes. Su ch models consist of grafting human glioblastoma cell lines, namely U8 7 and U373, into the brains of nude mice. However, while it is true th at experimental GBMs closely resemble the hGBMs with respect to some b iological characteristics, they also differ in many other significant biological characteristics.