Modulation of fas-mediated apoptosis in osteosarcoma cell lines.
Fas/APO-1 (or CD95) is a 45-kDa cell surface glycoprotein that transduces cellular death signals for apoptosis upon cross-linking with the Fas ligand, which is experimentally replaced by anti-Fas antibodies. We examined the Fas expression at the protein and mRNA levels, and susceptibility to anti-Fas-mediated apoptosis, in 14 osteosarcoma cell lines. Ten of 14 ostesarcoma cell lines constitutively expressed detectable levels of Fas on the cell surface with positive cell rates ranging from 10.2 to 72.4%. Four other cell lines expressed Fas almost exclusively in the cytoplasm. An antibody against Fas was able to induce Fas-mediated cell death only in two cell lines with high levels of surface Fas. In the presence of the protein synthesis inhibitor cyclohexamide, antibody to Fas led to an induction of apoptosis in ten of the osteosarcoma cell lines antibody-concentration dependently. These data suggest that Fas is a potential protein related to apoptosis in osteosarcomas when the sensitizing activity of cyclohexamide on anti-Fas-mediated cytotoxicity was exerted.
Hamada
T
T
Departments of Pathology and Orthopaedic Surgery, Kurume University School of Medicine, Kurume, Fukuoka 830-0011, Japan.
Komiya
S
S
Yano
H
H
Zenmyo
M
M
Hiraoka
K
K
Inoue
A
A
Morimatsu
M
M
D000911:Antibodies, Monoclonal / Q000494:pharmacology; D017209:Apoptosis; D002470:Cell Survival / Q000187:drug effects; D017077:Culture Media, Conditioned / Q000737:chemistry; D003513:Cycloheximide / Q000494:pharmacology; D018076:DNA, Complementary / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D014644:Genetic Variation; D006801:Humans; D007150:Immunohistochemistry; D012516:Osteosarcoma / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D020033:Protein Isoforms / Q000032:analysis / Q000235:genetics / Q000502:physiology; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D012334:RNA, Neoplasm / Q000235:genetics; D014407:Tumor Cells, Cultured; D019014:fas Receptor / Q000235:genetics / Q000276:immunology / Q000502:physiology*
D000911:Antibodies, Monoclonal; D017077:Culture Media, Conditioned; D018076:DNA, Complementary; D020033:Protein Isoforms; D011500:Protein Synthesis Inhibitors; D012334:RNA, Neoplasm; D019014:fas Receptor; D003513:Cycloheximide