DIFFERENTIAL EXPRESSION OF TRANSFORMING GROWTH FACTOR-BETA-1, FACTOR-BETA-2, AND FACTOR-BETA-3 BY GLIOBLASTOMA CELLS, ASTROCYTES, AND MICROGLIA

The type-beta transforming growth factors (TGF) are potent regulators of the growth and functions of lymphocytes and macrophages. Recently the human glioblastoma cell line 308 was shown to produce TGF-beta-2. The relevance of this finding was evaluated further by comparing human glioblastoma cells with their nontransformed animal counterpart, astrocytes, with regard to the production of the three TGF-beta isoforms observed so far in mammals. In this report astrocytes are demonstrated to secrete also TGF-beta-2 and to express TGF-beta-1, -beta-2, and -beta-3 mRNA in vitro. In contrast, cultured murine brain macrophages release TGF-beta-1 and are positive for TGF-beta-1 mRNA only. Glia cell-derived TGF-beta-1 and -beta-2 are detected in latent form whereas both latent and active TGF-beta are identified in the supernatant of three human glioblastoma cell lines tested. These cell lines, however, show heterogeneity in regard to the isoform of TGF-beta expressed but share with astrocytes the inability to release TGF-beta-3. Provided production and activation of latent TGF-beta occur in vivo, astrocytes and microglia may then be expected to exert regulatory influences on immune mediated diseases of the central nervous system.