Inhibition of Angiogenesis in Human Glioblastomas by Chromosome 10 Induction of Thrombospondin-1

摘要: Glioblastoma multiforme is distinguished from its less malignant astrocytoma precursors by intense angiogenesis and frequent loss of tumor suppressor genes on chromosome 10. Here we link these traits showing that when a wild-type 10 was returned to any three human glioblastoma cell lines U251, U87, or LG11, they lost their ability form tumors in nude mice switched an antiangiogenic phenotype, as measured the inhibition capillary endothelial migration corneal neovascularization. This change directly due increased secretion potent inhibitor angiogenesis, throm-bospondin-1, because: ( ) neutralizing thrombospondin completely relieved inhibition; b inhibitory activity not dependent transforming growth factor β; c introduction did alter secreted inducing activity. The vascular had ED50 µg/ml media conditioned parental cells 9–13 revertants. Normal astrocytes were also thrombospondin. effect production vitro reflected patient material. brain lower grade astrocytomas known retain stained strongly for thrombospondin, but 12 13 glioblastomas, majority which lose 10, not. These data indicate suppressors contributes aggressive malignancy glioblastomas part releasing constraints are maintained tumors.