Synergism between growth-factors in the control of glioma cell-proliferation, migration and invasion in-vitro.

Gliomas constitute more than 50% of primary brain tumours in man. Perhaps the most important hallmark of these tumours is their diffuse invasion of the normal brain structures. The biological factors involved in the control of both their proliferation and invasion are, however, not well known. We studied the expression of receptors for epidermal growth factor (EGF), basic fibroblast growth factor (bFGF), platelet derived growth factor (PDGF), and transforming growth factor beta-1 (TGF-beta 1) in low grade astrocytoma (IPNT-H)-, grade III astrocytoma (IPSB-18)-, and glioblastoma (IPRM-5)- derived cell lines. The effects of EGF, bFGF, PDGF, and TGF-beta 1 on proliferation, migration, and invasion in vitro were also investigated. When tested individually, EGF, bFGF and PDGF, were found to differentially stimulate proliferation, motility and invasion of the cell lines examined. When combined, these three growth factors acted synergistically to stimulate these biological properties. In addition, TGF-beta 1 exhibited positive and negative effects on the mitogenic action of the other growth factors in IPNT-H cells but inhibited their activity in IPSB-18 and IPRM-5 cells. Moreover, TGF-beta 1 was found to modulate negatively and positively the migration and invasion promoting action of the other growth factors in IPNT-H and IPSB-18 cells, while it strongly potentiated this action in IPRM-5 cells. These results suggest that all the growth factors examined may play key roles in the control of the biological properties of human glioma cells in vitro. Together with our findings that TGF-beta 1 is overexpressed in human glioblastoma in vivo, these results also suggest that co-operation between growth factors and TGF-beta 1 may be of central importance in tumour progression of gliomas.