Malignant glioma biology: role for TGF-beta in growth, motility, angiogenesis, and immune escape.
Characteristics of human malignant glioma are excessive proliferation, infiltrative growth, angiogenesis and suppression of anti-tumor immune surveillance. 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 growth factor (PDGF), metalloproteinases (MMP-2, MMP-9) and their inhibitor, plasmin activator inhibitor-1 (PAI-1), and immune cells, like natural killer cells, T-cells and microglia. The differential effects of TGF-beta in glioma biology are outlined with emphasis on the induction of a survival advantage for glioma cells by enforced cell growth, migration, invasion, angiogenesis and immune paralysis. By virtue of its growth regulatory and immunomodulatory properties, TGF-beta promises to become a novel target for the experimental therapy of human malignant glioma.
Platten
M
M
Department of Neurology, University of Tübingen, 72076 Tübingen, Germany. michael.platten@uni-tuebingen.de
Wick
W
W
Weller
M
M
D001932:Brain Neoplasms / Q000276:immunology / Q000503:physiopathology; D005910:Glioma / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D009389:Neovascularization, Pathologic; D016212:Transforming Growth Factor beta / Q000502:physiology*; D019139:Tumor Escape
D016212:Transforming Growth Factor beta