Induction of intercellular adhesion molecule-1 by Fas ligation: proinflammatory roles of Fas in human astroglioma cells

Abstract

FasL has been shown to induce angiogenesis in vivo, however, the mechanism remains to be determined. We have previously shown that Fas ligation induces expression of chemokines such as interleukin-8 by human astrogliomas, which may partially explain the in vivo angiogenic property of FasL. Intercellular adhesion molecule (ICAM)-1 is increased in various human tumors, and is thought to be involved in the processes of metastasis and angiogenesis. We demonstrate that Fas ligation induces ICAM-I expression at the mRNA and protein levels in human astroglioma cells. Studies using Boc-D-Fmk, a pharmacological inhibitor, show that caspase activation is required for Fas-mediated ICAM-1 induction. To study the in vivo expression of Fas and ICAM-1, human low-grade astrogliomas and glioblastoma multiforme (GBM) samples were examined by ELISA for Fas and ICAM-1. Human GBM samples express higher levels of Fas compared to normal control brain, which correlates with increased ICAM-1 expression. These findings suggest that Fas ligation on human glioma cells leads to the induction of ICAM-1 expression, which involves caspase cascade signaling pathways. (C) 2003 Elsevier Ireland Ltd. All rights reserved.