Gene transfer of Fas ligand induces tumor regression in vivo
Gene transfer of Fas ligand induces tumor regression in vivo
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DOI：
10.1073/pnas.94.25.13862
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发表时间：
1997-12-09
影响因子：
11.1
通讯作者：
Nabel, GJ
中科院分区：
文献类型：
--
作者：
Arai, H;Gordon, D;Nabel, GJ
Fas-Fas配体(Fas-Fas Ligand，FasL)系统在诱导淋巴细胞凋亡中发挥重要作用，并参与免疫反应的抑制。在此，我报道了FasL基因转移在体内抑制肿瘤细胞的生长。虽然这种抑制作用在Fas(+)肿瘤细胞系中是预期的，但在将FasL基因转移到不表达Fas的CT26结肠癌后，却意外地观察到显著的消退。感染Fas(+)Renca瘤体内的Fas(+)的腺病毒载体通过诱导细胞死亡而迅速清除肿瘤肿块，而Fas(-)CT26细胞的清除是由炎症细胞介导的。对人类恶性肿瘤的分析显示，Fas在大多数肿瘤中表达，但不是Fast，在大多数Fas(+)细胞系中对Fast易感性。这些发现表明，FAST的基因转移会产生凋亡反应，并诱导强烈的炎症反应，可用于诱导恶性肿瘤的消退。
The Fas-Fas ligand (FasL) system plays an important role in the induction of lymphoid apoptosis and has been implicated in the suppression of immune responses. Herein, me report that gene transfer of FasL inhibits tumor cell growth in vivo. Although such inhibition is expected in Fas(+) tumor cell lines, marked regression was unexpectedly observed after FasL gene transfer into the CT26 colon carcinoma that does not express Fas. Infection by an adenoviral vector encoding Fast rapidly eliminated tumor masses in the Fas(+) Renca tumor by inducing cell death, whereas the elimination of Fas(-) CT26 cells was mediated by inflammatory cells. Analysis of human malignancies revealed Fas, but not Fast, expression in a majority of tumors and susceptibility to Fast in most Fas(+) cell lines. These findings suggest that gene transfer of Fast generates apoptotic responses and induces potent inflammatory reactions that can be used to induce the regression of malignancies.