Owen-Schaub L B, van Golen K L, Hill L L, Price J E
Department of Immunology, University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030, USA.
J Exp Med. 1998 Nov 2;188(9):1717-23. doi: 10.1084/jem.188.9.1717.
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.
Fas（CD95）连接诱导的细胞凋亡在肿瘤进展过程中常常丧失；然而，尚无直接证据支持Fas功能丧失与转移性肿瘤行为之间存在关联。为了确定Fas功能丧失对于获得转移表型是否至关重要，我们比较了Fas敏感的K1735小鼠黑色素瘤在野生型和Fas配体缺陷型小鼠中形成自发性肺转移的能力。Fas敏感的黑色素瘤克隆具有高度致瘤性，但在野生型同基因小鼠中很少发生转移。然而，在Fas配体缺陷型小鼠中，转移的发生率和数量均增加。这些发现提供了首个证据，表明Fas-Fas配体相互作用可抑制转移，且肿瘤Fas功能丧失可能与转移进展存在因果关系。
