Cytotoxic T-lymphocytes secrete soluble factors that induce caspase-mediated apoptosis in glioblastoma cell lines.
We have previously shown that factors secreted by activated CTLs induce apoptosis in a panel of glioblastoma lines. In this study, we analyzed the expression of death receptors, activation of caspases and mRNA expression of 96 apoptotic genes in glioblastoma lines either sensitive or resistant to supernatant of activated CTLs. Our results indicate that exposure to supernatant triggers several pathways of caspase activation in glioblastoma lines involved in the initiation of both extrinsic and intrinsic apoptosis. High steady-state levels of Bcl-2 were identified as potentially accounting for the resistance of a proportion of glioblastoma lines to factors secreted by activated CTLs.
Cagigi
Alberto
A
Department of Laboratory Medicine, Division of Clinical Immunology, Karolinska University Hospital Huddinge, Stockholm, Sweden. Alberto.Cagigi@ki.se
Nilsson
Anna
A
Levitsky
Victor
V
Sabri
Farideh
F
D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D017304:Annexin A5 / Q000378:metabolism; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D020169:Caspases / Q000235:genetics / Q000378:metabolism*; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D005434:Flow Cytometry / Q000379:methods; D020869:Gene Expression Profiling / Q000379:methods; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects / Q000502:physiology*; D005909:Glioblastoma / Q000378:metabolism / Q000503:physiopathology*; D006801:Humans; D016014:Linear Models; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000378:metabolism*; D013997:Time Factors; D014162:Transfection / Q000379:methods; D014407:Tumor Cells, Cultured; D019014:fas Receptor / Q000276:immunology
D000590:Amino Acid Chloromethyl Ketones; D017304:Annexin A5; D000911:Antibodies, Monoclonal; D015853:Cysteine Proteinase Inhibitors; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; D019014:fas Receptor; D020169:Caspases