Malignant glioma biology: Role for TGF-beta in growth, motility, angiogenesis, and immune escape

Characteristics of human malignant glioma are excessive proliferation, infi ltrative growth, angiogenesis and suppression of anti-tumor immune surveill ance. Transforming growth factor-beta (TGF-beta), a versatile cytokine, is intimately involved in the regulation of these processes. Here, we discuss the interactions of TGF-beta with growth factors, such as basic fibroblast growth factor (bFGF), epidermal growth factor (EGF) and platelet derived gr owth factor (PDGF), metalloproteinases (MMP-2, MMP-9) and their inhibitor, plasmin activator inhibitor-1 (PAI-1), and immune cells, like natural kille r cells, T-cells and microglia. The differential effects of TGF-beta in gli oma biology are outlined with emphasis on the induction of a survival advan tage for glioma cells by enforced cell growth, migration, invasion, angioge nesis and immune paralysis. By virtue of its growth regulatory and immunomo dulatory properties, TGF-beta promises to become a novel target for the exp erimental therapy of human malignant glioma. Microsc. Res. Tech. 52:401-410 , 2001. (C) 2001 Wiley-Liss, Inc.