FAS APO-1 EXPRESSION AND FUNCTION ON MALIGNANT-CELLS OF HEMATOLOGIC AND NONHEMATOLOGIC ORIGIN
FAS APO-1 EXPRESSION AND FUNCTION ON MALIGNANT-CELLS OF HEMATOLOGIC AND NONHEMATOLOGIC ORIGIN
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DOI：
10.1097/00002371-199310000-00011
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发表时间：
1993-10-01
影响因子：
3.9
通讯作者：
FORD, RJ
中科院分区：
文献类型：
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作者：
OWENSCHAUB, LB;METERISSIAN, S;FORD, RJ
Fas/APO-1是一种细胞表面蛋白，能够在特异性抗体结合后诱导多种细胞类型的凋亡。抗Fas/APO-1抗体已成功用于治疗小鼠的几种淋巴恶性肿瘤。在抗Fas诱导的细胞凋亡被充分利用作为临床治疗之前，Fas/APO-1的分布、功能和调节必须进一步研究。在这项研究中，我们分析了新鲜分离的B细胞和T细胞淋巴瘤以及非血液肿瘤细胞系的Fas/APO-1表达和抗Fas的生长抑制作用的敏感性。组成型Fas/APO-1表达在非常低的水平上，只有一个的8个B细胞淋巴瘤分析。然而，通过与高分子量B细胞生长因子（HMW-BCGF）一起培养，表达显着上调。Fas/APO-1组成型表达的两个T细胞淋巴瘤检查的水平相当的活化正常淋巴细胞。然而，Fas/APO-1表达阳性的B细胞淋巴瘤和T细胞淋巴瘤均未被抗Fas抗体抑制生长。此外，在一例HMW-BCGF激活的B细胞淋巴瘤中，抗Fas治疗后观察到显著的生长增强。非血液肿瘤细胞系显示出抗Fas的生物反应谱相似，生长受到抑制，生长受到刺激或不受抗体治疗的影响。总之，这些研究表明，Fas/APO-1的参与可能会引发不同的生物学效应谱，与神经生长因子受体/肿瘤坏死因子受体超家族的其他成员没有什么不同。
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.