Background: The prognosis of children with malignant gliomas is poor. A new therapeutic strategy using interferon-gamma (IFN-g) as an immunostimulator substance will start in Germany in 1997. One of the therapeutic problems in malignant gliomas is the high invasiveness of the tumor cells. Adhesion to the extracellular matrix molecule hyaluronic acid (HA) is involved in invasion. We addressed the question of whether IFN-g (i) influences the proliferation and (ii) changes the HA-binding capacity of malignant glioma cells.
Method: T98G glioblastoma cells were incubated up to 4 days with IFN-g (30 and 300 IE/ml). Proliferation was measured by a colorimetric assay (MTT) and compared with untreated controls. Expression of the HA-receptor CD44 was determined by FACS-analysis using the mouse monoclonal antibody J-173. HA-adhesion was investigated using HA-coated (3 mg/ml), bovine serum albumin blocked 24-well-plates and compared with uncoated wells.
Results: FN-g (300 IE/ml) inhibited proliferation to 76.3% (p < 0.0001) after 48 hours compared with untreated controls. This effect was mediated not only by inhibition of proliferation, but also by induction of cell-death, first seen 72 h after IFN-g incubation. 24 hours later only 24% of treated cells survived. 93.1% of T98G cells expressed CD44 (FACS-analysis). A specific HA-adhesion of glioma cells was shown: 85.5% of the cells adhered to HA, 13.3% to BSA compared with controls. 300 IE/ml IFN-g decreased HA-adhesion significantly (p < 0.001) to 17%, whereas BSA-adhesion remained unchanged.
Conclusion: IFN-g inhibits tumor cell proliferation and diminishes the invasive properties of glioma cells via reduction of HA binding capacity. Our results support the use of IFN-g in the therapy of malignant gliomas.