IN-SITU DETECTION OF TRANSFORMING GROWTH-FACTOR-BETA MESSENGER-RNA IN EXPERIMENTAL RAT GLIOMA AND REACTIVE GLIAL-CELLS

Malignant gliomas are associated with a state of systemic immunosuppression which appears to be partially mediated by transforming growth factor beta (TGF-beta) secreted from glioma cells. In a recently described animal model of malignant glioma, massive activation of local microglial cells and formation of microglia-derived macrophages has been observed in the absence of detectable tumour regression. We have investigated the in situ expression of TGF-beta in rat glioma as a possible cause of ineffective tumour destruction. Two weeks following unilateral injection of glioma cells, large tumours were observed in the affected hemisphere. In situ hybridization for TGF-beta 1 mRNA revealed an intense signal over the entire tumour area. In the peritumoural area, at sites of glial activation, a lower signal was obtained over cellular profiles containing nuclei typical for microglia, as well as other unidentified cellular profiles. No signal was obtained over the contralateral unaffected hemisphere. Northern blot analysis revealed a strong expression of TGF-beta 1 mRNA in tumour tissue, a lesser signal in the peritumoural reactive brain tissue and virtually no signal in normal tissue. Our data indicate that the experimental rat glioma has the potential to secrete TGF-beta in vivo which might render the microglial infiltration ineffective. TGF-beta expressed by activated microglial cells themselves might further inhibit their tumoricidal potential, thus contributing further to unrestrained tumour growth.