Merzak A, Koochekpour S, Dkhissi F, Raynal S, Lawrence D, Pilkington G
INST CURIE,F-91405 ORSAY,FRANCE. UNIV MOULAY ISMAIL,FAC SCI,DEPT BIOL,MEKNES,MOROCCO.
Int J Oncol. 1995 May;6(5):1079-85. doi: 10.3892/ijo.6.5.1079.
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.
神经胶质瘤占人类原发性脑肿瘤的50%以上。这些肿瘤最重要的特征或许是它们对正常脑结构的弥漫性侵袭。然而，参与控制其增殖和侵袭的生物学因素尚不清楚。我们研究了表皮生长因子（EGF）、碱性成纤维细胞生长因子（bFGF）、血小板衍生生长因子（PDGF）和转化生长因子β-1（TGF-β1）在低级别星形细胞瘤（IPNT-H）、三级星形细胞瘤（IPSB-18）和胶质母细胞瘤（IPRM-5）来源的细胞系中的受体表达。还研究了EGF、bFGF、PDGF和TGF-β1对体外增殖、迁移和侵袭的影响。单独测试时，发现EGF、bFGF和PDGF对所检测的细胞系的增殖、运动性和侵袭有不同的刺激作用。当联合使用时，这三种生长因子协同作用以刺激这些生物学特性。此外，TGF-β1对IPNT-H细胞中其他生长因子的促有丝分裂作用表现出正负两种效应，但在IPSB-18和IPRM-5细胞中抑制其活性。此外，发现TGF-β1在IPNT-H和IPSB-18细胞中对其他生长因子的迁移和侵袭促进作用有正负调节作用，而在IPRM-5细胞中则强烈增强这种作用。这些结果表明，所检测的所有生长因子可能在体外控制人胶质瘤细胞的生物学特性中起关键作用。连同我们在体内人胶质母细胞瘤中TGF-β1过表达的发现，这些结果还表明生长因子与TGF-β1之间的合作可能在胶质瘤的肿瘤进展中至关重要。
