Fas and Fas ligand interactions suppress melanoma lung metastasis.
Fas and Fas ligand interactions suppress melanoma lung metastasis.
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DOI：
10.1084/jem.188.9.1717
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发表时间：
1998-11-02
期刊：
影响因子：
--
通讯作者：
Price JE
中科院分区：
文献类型：
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作者：
Owen-Schaub LB;van Golen KL;Hill LL;Price JE
Fas（CD 95）连接诱导的细胞凋亡在肿瘤进展过程中经常丢失;然而，没有直接证据支持Fas功能丧失与转移性肿瘤行为的关联。为了确定Fas功能丧失是否是获得转移表型的关键，我们比较了Fas敏感性K1735小鼠黑色素瘤在野生型和Fas配体缺陷小鼠中形成自发性肺转移的能力。Fas敏感的黑色素瘤克隆是高度致瘤性的，但在野生型同基因小鼠中很少转移。然而，在Fas配体缺陷小鼠中，转移的发生率和数量均增加。这些发现提供了第一个证据表明，Fas-Fas配体相互作用可以抑制转移，肿瘤Fas功能丧失可能与转移进展有因果关系。
Apoptosis induced by Fas (CD95) ligation is frequently lost during tumor progression; however, there is no direct evidence to support an association of Fas loss-of-function with metastatic tumor behavior. To determine whether Fas loss-of-function is critical for acquisition of the metastatic phenotype, we have compared the ability of Fas-sensitive K1735 murine melanomas to form spontaneous lung metastases in wild-type and Fas ligand–deficient mice. Fas-sensitive melanoma clones are highly tumorigenic but rarely metastatic in wild-type syngeneic mice. However, in Fas ligand–deficient mice, both the incidence and number of metastases are increased. These findings provide the first evidence that Fas–Fas ligand interactions can suppress metastasis and that tumor Fas loss-of-function may be causally linked to metastatic progression.