CAN EXPERIMENTAL-MODELS OF RODENT IMPLANTATION GLIOMA BE IMPROVED - ASTUDY OF PURE AND MIXED GLIOMA CELL-LINE TUMORS

To evaluate the hypothesis that co-implantation of different rodent gl ioma cell lines might result in experimental brain tumours that more c losely resemble human gliomas the neuropathology and immunocytochemica l features of implantation gliomas derived from single cell lines (C6, A15A5, F98), two cell lines admired 50:50 prior to implantation (C6 F98 and C6 + A15A5) and three cell lines equally admired (C6 + A15A5 + F98) was studied in the adult Wistar rat. Tumours grew consistently following implantation of the single and the two admired cell lines, h owever tumour growth following triple mix implantation was considerabl y and consistently impaired. The tumours derived from admired cell lin es showed regional heterogeneity with areas characteristic of both the primary cell lines. Foci of lymphocytic infiltrates, tumoural necrosi s, often with pseudopallisading, and peritumoural edema were consisten t features of all tumours. Limited parenchymal and more extensive peri vascular tumoural invasion was seen predominantly in tumours containin g the C6 cell line. There were no significant differences in GFAP, vim entin and HSP70 staining between the mixed tumours, although the pure F98 and A15A5 tumours were, unlike the pure C6 gliomas, S-100 negative . Using PCNA expression as a measure of the tumour proliferation all e xcept the tumours derived from the three cell lines mix, which had a s taining index of 7-10 %, had focal staining indices in viable tumour o f between 40-80 %. There was focal positive staining in both perilesio nal brain and in regions of all tumours for the macrophage markers ED- 1 and ED-2. None of the three cell lines stained in vitro for either E D1 and ED2 but all were constitutively positive in vitro for OX-6, a p roposed marker for antigen presenting cells. The macrophage and lympho cytic response suggest a vigorous but largely ineffective immunologica l response had been mounted against all rumours. The consistent failur e of the triple mix tumours to grow is unexplained. This work has show n the feasibility of producing 'mixed' cell line experimental gliomas by combining two cell lines at the time of innoculation. However, the relative failure to produce (i) mixed tumours that have properties not inherent to either parent cell line and (ii) implantation glioma with three cell lines suggest there are limits to this approach. Admixture of cell lines at the time of implantation therefore does not make exp erimental glioma models that more closely resemble natural gliomas, an d also has some particular disadvantages. This experimental approach i s therefore not recommended for use in the study of tumour biology and in evaluating the effectiveness of novel therapies.