Contribution of CD95 Ligand-Induced Neutrophil Infiltration to the Bystander Effect in p53 Gene Therapy for Human Cancer1
Contribution of CD95 Ligand-Induced Neutrophil Infiltration to the Bystander Effect in p53 Gene Therapy for Human Cancer1
复制标题
CD95 配体诱导的中性粒细胞浸润对人类癌症 p53 基因治疗中旁观者效应的贡献1
作者：
T. Waku;T. Fujiwara;Jianghua Shao;T. Itoshima;T. Murakami;M. Kataoka;S. Gomi;J. Roth;Noriaki Tanaka
腺病毒p53基因治疗的临床试验证明，野生型p53基因转移到邻近肿瘤细胞诱导的旁观者效应有助于肿瘤的进展；然而，其机制尚不清楚。我们在这项工作中报道，将表达人类野生型p53基因（Ad5CMVp53）的腺病毒注射到nu/nu小鼠已建立的人类结直肠肿瘤中，导致CD95配体（CD95L）过表达，随后出现大量中性粒细胞浸润。感染Ad5CMVp53的人结直肠癌细胞培养上清对小鼠多形核中性粒细胞具有强效趋化活性，可被抗cd95l单抗（NOK-1）消除。体内细胞耗竭实验表明，中性粒细胞在Ad5CMVp53感染的抗肿瘤作用中起部分作用。我们的数据直接提示，野生型p53基因转染过表达CD95L可诱导中性粒细胞浸润到人结直肠肿瘤中，这可能在p53基因治疗的旁观者效应中起关键作用。
Clinical trials of adenoviral p53 gene therapy provide the evidence that the bystander effect induced by the wild-type p53 gene transfer on adjacent tumor cells contributes to tumor progression; its mechanism, however, remains uncharacterized. We report in this work that injection of adenovirus expressing the human wild-type p53 gene (Ad5CMVp53) into established human colorectal tumors in nu/nu mice resulted in CD95 ligand (CD95L) overexpression, followed by a massive neutrophil infiltration. Culture supernatants of human colorectal cancer cells infected with Ad5CMVp53 exhibited a potent chemotactic activity against murine polymorphonuclear neutrophils, which could be abolished by the anti-CD95L mAb (NOK-1). In vivo cell depletion experiments indicated that neutrophils were in part responsible for the antitumor effect of the Ad5CMVp53 infection. Our data directly suggest that overexpression of CD95L by the wild-type p53 gene transfer induces neutrophil infiltration into human colorectal tumors, which may play a critical role in the bystander effect of p53 gene therapy.
重组腺病毒介导的人肺癌细胞中野生型p53的高效基因转移和高水平表达。
影响因子：
6.4
作者：
Zhang,WW;Fang,X;Mazur,W;French,BA;Georges,RN;Roth,JA
通讯作者：
Roth,JA
DOI：
10.1073/pnas.94.25.13862
发表时间：
1997-12-09
影响因子：
11.1
作者：
Arai, H;Gordon, D;Nabel, GJ
通讯作者：
Nabel, GJ