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Background: Various immunotherapeutical approaches are presently evaluated for their efficacy to eradicate glioma cells. Complicating the concepts, these tumors secrete cytokines which modulate the immune response., Materials & Methods: We analyzed the influence of interferon gamma (IFN-gamma) on the cytokine production and IFN-gamma receptor expression in T98G and U87-MG human glioma cells., Results: The IFN-gamma receptors were own-regulated after IFN-gamma treatment. Secretion of interleukin-6 (IL-6) protein was elevated by factors of 6.4 in T98G cells and 5.2 in U87-MG. Other cytokines were increased as well, but less constantly: IL-8, and VEGF were elevated significantly only in T98G, but not in U87-MG. Increases of IL-1 beta, IL-1 alpha and TGF beta-2 were only detectable at the mRNA level. TNF was not detectable in any of the cell lines, and TGF-beta, alpha FGF and HG were not influenced by IFN-gamma., Conclusion: IL-6 produced by glioma cells in response to IFN-gamma might support immune eradication of glioma cells.

The mechanisms underlying the rapid invasive growth of malignant gliomas are poorly understood. Adhesion to extracellular hyaluronic acid (HA) has been implicated in the invasive properties of tumor cells. We investigated the HA binding capacity of human (T98G, A172, U87MG, 86HG39, 85HG66) and rat (C6, 9L) glioma cell lines by means of HA coated, bovine serum albumin (BSA)-blocked (HA/BSA) and only BSA-blocked culture plates. Results were compared with adhesion to native wells (100% adhesion). Adhesion to HA/BSA was high for T98G (84.4%), medium for 86HG39 (36%), 9L (33.1%), A172 (35.5%) and low for 85HG66 (21.3%) and U87MG (26.8%). Adhesion to only BSA-coated wells was significantly lower in all these cell lines, suggesting a specific HA-adhesion. Only C6 showed similar adhesion to HA/BSA and BSA alone, therefore, C6 failed to bind HA specifically. These results suggest that adhesion to extracellular HA might be involved in the invasion of some gliomas.

Malignant gliomas are relatively resistant to radiation and chemotherapy. To investigate whether cisplatin (cis-diamminedichloroplatinum(II), CDDP) causes resistance we pretreated C6 cells with 10(-6) M CDDP for 24 hours and then tested their sensitivity in a colorimetric assay. Pretreated cells developed resistance to CDDP (resistance factor 2.0) and radiation (survival after 9 Gy 60Co: 36.4% +/- 5.5 versus 28.6% +/- 5.2, p = 0.005). Glutathione levels of pretreated cells were higher (51.7 +/- 13.8 ng/mg protein) than in wt cells (40.4 +/- 13.2, p = 0.029). Addressing the mechanisms we established 4 wild type subclones with different CDDP sensitivities. However, cross-resistance to CDDP (survival: 60.7% +/- 3.5 versus 7.2% +/- 0.5, respectively p = < 0.001) and radiation (29.7% +/- 2.6 versus 12.9% +/- 0.8, p = < 0.001) could also be induced in a subclone showing involvement of mutation. These data suggest that CDDP can induce resistance mediated via induced mutation and increased GSH levels.

Malignant gliomas are often treated with cisplatin (cis-diamminedichloroplatinum(II), CDDP) and radiation but results remain unsatisfactory. To investigate whether CDDP induces radioresistance in glioma, T98G human glioblastoma cells were pretreated 5 times with 10(-6)M CDDP for 24 hours and then the sensitivity of wild type (wt) and pretreated cells towards radiation (9Gy 60Co) and CDDP was tested in a colorimetric assay (MIT). The growth rates of wt and pretreated cells were 1.8 +/-0.2 and 3.1 +/- 0.2 respectively (p = 0.000155) 216 hours post radiation. Pretreated cells also developed resistance to CDDP (resistance factor 2.35). Glutathione (GSH) which potentially mediates resistance to both treatments was measured. Incubation for 6 hours with 10(-5) M CDDP increased GSH levels by a factor of 2.28 (p < 0.0001). However, neither basal nor increased levels differed between wt and pretreated cells. These data show that CDDP pretreatment can induce resistance against radiation and CDDP independently of GSH.