Fas/APO-1 expression and function on malignant cells of hematologic and nonhematologic origin.
Fas/APO-1 is a cell-surface protein capable of inducing apoptosis in a variety of cell types upon specific antibody engagement. Antibodies against Fas/APO-1 have been used successfully for the treatment of several lymphoid malignancies in mice. Before apoptosis triggered by anti-Fas can be fully exploited as a clinical therapy, Fas/APO-1 distribution, function, and regulation must be further studied. In this study, we analyzed freshly isolated B-cell and T-cell lymphomas as well as nonhematological tumor cell lines for Fas/APO-1 expression and sensitivity to the growth-inhibitory effects of anti-Fas. Constitutive Fas/APO-1 was expressed at very low levels on only one of eight B-cell lymphomas analyzed. Expression was markedly up-regulated, however, by culture with high-molecular-weight B-cell growth factor (HMW-BCGF). Fas/APO-1 was constitutively expressed on one of two T-cell lymphomas examined at levels comparable to those of activated normal lymphocytes. However, neither the B-cell nor T-cell lymphomas positive for Fas/APO-1 expression were growth inhibited by anti-Fas. Furthermore, in the case of one HMW-BCGF-activated B-cell lymphoma, a significant growth enhancement was observed upon anti-Fas treatment. Nonhematologic tumor cell lines showed a similar spectrum of biologic responses to anti-Fas, being growth inhibited, growth stimulated or unaffected by antibody treatment. In summary, these studies suggest that engagement of Fas/APO-1 may trigger a diverse spectrum of biologic effects not unlike other members of the nerve growth factor receptor/tumor necrosis factor receptor superfamily.
Owen-Schaub
L B
LB
Department of Immunology, University of Texas M. D. Anderson Cancer Center, Houston 77030.
Meterissian
S
S
Ford
R J
RJ
D000951:Antigens, Neoplasm / Q000032:analysis*; D000954:Antigens, Surface / Q000032:analysis*; D017209:Apoptosis / Q000276:immunology*; D006801:Humans; D016393:Lymphoma, B-Cell / Q000276:immunology; D008228:Lymphoma, Non-Hodgkin / Q000276:immunology* / Q000473:pathology; D016399:Lymphoma, T-Cell / Q000276:immunology; D008565:Membrane Proteins / Q000032:analysis*; D015398:Signal Transduction / Q000276:immunology*; D014407:Tumor Cells, Cultured; D019014:fas Receptor
D000951:Antigens, Neoplasm; D000954:Antigens, Surface; D008565:Membrane Proteins; D019014:fas Receptor