Expression and functional activity of osteoprotegerin in human malignant gliomas.
Apo2L/TRAIL-based therapy is a promising experimental approach to the treatment of human malignant gliomas. Osteoprotegerin (OPG) is a soluble decoy receptor for Apo2L/TRAIL that antagonizes Apo2L/TRAIL-induced apoptosis. High levels of OPG expressed by tumor cells might therefore abrogate the activity of exogenously added or adenovirally expessed Apo2L/TRAIL. Here we assessed the expression of OPG in human gliomas in vivo, in primary glioma cell cultures and in established glioma cell lines. Immunohistochemistry revealed weak OPG immunoreactivity in up to 5% of the tumor cells in 8 of 13 glioblastomas. Strong OPG labeling was detected in single scattered tumor cells in one of these specimens. Five glioblastomas did not express OPG. High OPG expression was found in 1 of 6 primary glioma cell cultures and in 1 of 12 established glioma cell lines, T98G. OPG released by T98G cells was biologically active in that it inhibited Apo2L/TRAIL-induced apoptosis in sensitive glioma cells. Altogether, however, these data suggest that OPG expression may not be a major pathway of glioma cell resistance to future Apo2L/TRAIL-based therapeutic approaches.
D017209:Apoptosis / Q000187:drug effects; D051017:Apoptosis Regulatory Proteins; D001932:Brain Neoplasms / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005910:Glioma / Q000378:metabolism*; D006023:Glycoproteins / Q000378:metabolism*; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D008562:Membrane Glycoproteins / Q000378:metabolism; D053244:Osteoprotegerin; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D018124:Receptors, Tumor Necrosis Factor; D020133:Reverse Transcriptase Polymerase Chain Reaction; D053221:TNF-Related Apoptosis-Inducing Ligand; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D051017:Apoptosis Regulatory Proteins; D006023:Glycoproteins; D008562:Membrane Glycoproteins; D053244:Osteoprotegerin; D018160:Receptors, Cytoplasmic and Nuclear; D018124:Receptors, Tumor Necrosis Factor; D053221:TNF-Related Apoptosis-Inducing Ligand; C506030:TNFRSF11B protein, human; C505653:TNFSF10 protein, human; D014409:Tumor Necrosis Factor-alpha