CONTROL OF HUMAN GLIOMA CELL-GROWTH, MIGRATION AND INVASION IN-VITRO BY TRANSFORMING GROWTH-FACTOR BETA(1)

Factors involved in the control of the biological properties of glioma s, the major form of brain tumour in man, are poorly documented. We in vestigated the role of transforming growth factor beta(1) (TGF-beta(1) ) in the control of proliferation of human glioma cell lines as well a s normal human fetal brain cells. The data presented show that TGF-bet a(1) exerts a growth-inhibitory action on both human fetal brain cells and three cell lines derived from human glioma of different grades of malignancy. In addition, this growth-inhibitory effect is dose depend ent and serum independent. Since TGF-beta(1) is known to be involved i n the control of cell migration during ontogenesis and oncogenesis, we investigated the role of this factor in the motile and invasive behav iour that characterises human gliomas in vivo. TGF-beta(1) was found t o elicit a strong stimulation of migration and invasiveness of glioma cells in vitro. In combination with recent data showing an inverse cor relation between TGF-beta(1) expression in human gliomas and survival, these findings may suggest that TGF-beta(1) plays an important role i n the malignant progression of gliomas in man. A study of the molecula r mechanisms involved in the antiproliferative action and the invasion -promoting action of TGF-beta(1) may help to identify new targets in t herapy for brain tumours. A combined antiproliferative and anti-invasi ve therapy could be envisaged.