title: Soluble TNF-alpha receptors are constitutively shed and downregulate adhesion molecule expression in malignant gliomas.
abstract: The regulation of adhesion molecule expression in malignant gliomas by tumor necrosis factor-alpha (TNF) and soluble TNF receptors (TNFR) was examined in the malignant glioma cell line A-172 and in 2 primary glioblastoma cell cultures (LA-492 and LA-567). A-172 cells expressed only the p55 TNF receptor transcripts and protein. The 2 primary cell cultures expressed both the p55 and p75 TNF receptors. In A-172 cells and in 1 of 2 primary glioma cell cultures, TNF upregulated the expression of ICAM-1 and VCAM-1, A-172 and both primary glioma cultures also shed their TNF receptors in the absence of activation by stimulating agents. Soluble p55 (sp55) receptors, but not soluble p75 (sp75) receptors, were found to reduce the TNF induced VCAM-1 and ICAM-1 expression in both the glioma cell line and the primary cell culture. Immunostaining of malignant glioma sections confirmed the presence of soluble TNFR and adhesion molecule expression in glioma cells in situ. These data suggest that soluble TNF receptors may play a role in the mechanism by which malignant gliomas downregulate the effects of infiltrating immune-competent cells.
authors.affiliation: Department of Neurosurgery, University of Southern California School of Medicine, USA.
authors.forename: T C
authors.initials: TC
authors.lastname: Chen
authors.forename: D R
authors.initials: DR
authors.lastname: Hinton
authors.forename: B D
authors.initials: BD
authors.lastname: Sippy
authors.forename: F M
authors.initials: FM
authors.lastname: Hofman
mesh_terms: D015815:Cell Adhesion Molecules / Q000378:metabolism*; D005910:Glioma / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D039041:Integrin alpha4beta1; D016023:Integrins / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D016201:Receptors, Lymphocyte Homing / Q000378:metabolism; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism* / Q000502:physiology*; D012995:Solubility; D014018:Tissue Distribution; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
chemical_list: D015815:Cell Adhesion Molecules; D039041:Integrin alpha4beta1; D016023:Integrins; D016201:Receptors, Lymphocyte Homing; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1