Increased susceptibility to tumor initiation and metastasis in TNF-related apoptosis-inducing ligand-deficient mice
Increased susceptibility to tumor initiation and metastasis in TNF-related apoptosis-inducing ligand-deficient mice
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DOI：
10.4049/jimmunol.168.3.1356
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发表时间：
2002-02-01
影响因子：
4.4
通讯作者：
Smyth, MJ
中科院分区：
文献类型：
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作者：
Cretney, E;Takeda, K;Smyth, MJ
我们以前曾暗示肿瘤坏死因子相关凋亡诱导配体（TRAIL）在先天免疫监视肿瘤的发展。在这项研究中，我们描述了使用TRAIL基因靶向小鼠来证明TRAIL在抑制肿瘤发生和转移中的关键作用。来自TRAIL基因靶向小鼠的肝和脾单核细胞缺乏TRAIL表达和TRAIL介导的细胞毒性。TRAIL基因靶向小鼠对实验性和自发性肿瘤转移更敏感，并且α-半乳糖神经酰胺在TRAIL基因靶向小鼠中的免疫抑制价值降低。TRAIL基因靶向小鼠对化学致癌物甲基霍蒽也更敏感。这些结果证实了TRAIL作为一种重要的天然效应分子用于宿主防御转化细胞。
We have previously implicated TNF-related apoptosis-inducing ligand (TRAIL) in innate immune surveillance against tumor development. In this study, we describe the use of TRAIL gene-targeted mice to demonstrate the key role of TRAIL in suppressing tumor initiation and metastasis. Liver and spleen mononuclear cells from TRAIL gene-targeted mice were devoid of TRAIL expression and TRAIL-mediated cytotoxicity. TRAIL gene-targeted mice were more susceptible to experimental and spontaneous tumor metastasis, and the immunotherapeutic value of alpha-galactosylceramide was diminished in TRAIL gene-targeted mice. TRAIL gene-targeted mice were also more sensitive to the chemical carcinogen methyleholanthrene. These results substantiated TRAIL as an important natural effector molecule used in the host defense against transformed cells.