Suppression of peritoneal implantation of gastric cancer cells by adenovirus vector-mediated NK4 expression
Suppression of peritoneal implantation of gastric cancer cells by adenovirus vector-mediated NK4 expression
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DOI：
10.1038/sj.cgt.7700782
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发表时间：
2005-02
影响因子：
6.4
通讯作者：
H. Fujiwara;T. Kubota;H. Amaike;S. Inada;Kazuhiro Takashima;K. Atsuji;M. Yoshimura;M. Maemondo;K. Narumi;T. Nukiwa;Kunio Matsumoto;Toshikazu Nakamura;A. Hagiwara;H. Yamagishi
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文献类型：
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作者：
H. Fujiwara;T. Kubota;H. Amaike;S. Inada;Kazuhiro Takashima;K. Atsuji;M. Yoshimura;M. Maemondo;K. Narumi;T. Nukiwa;Kunio Matsumoto;Toshikazu Nakamura;A. Hagiwara;H. Yamagishi
腹膜播散是胃癌最常见的转移方式。我们以前曾报道过乳斑（MS），腹膜淋巴组织，作为腹膜转移中肿瘤种植的选择性位点的重要性。在本研究中，我们首先证明，腹腔注射腺病毒载体编码的GFP基因到无瘤裸鼠导致GFP在网膜和肠系膜MS的表达; MS巨噬细胞是腺病毒感染的靶细胞。我们证实，腹腔注射腺病毒载体编码的NK 4基因（AdNK 4）导致NK 4生产定位于腹腔，特别是网膜。腺病毒载体介导的MS选择性转基因表达在MS已经被浸润性癌细胞取代的荷瘤小鼠中明显受损。然而，预先注射AdNK 4成功抑制了MS选择性癌细胞植入，从而抑制了腹膜传播并延长了生存期。腺病毒载体介导的治疗基因的MS选择性递送可以防止胃癌的腹膜传播。
Peritoneal dissemination is the most common mode of metastasis in gastric cancer. We previously reported the importance of milky spots (MS), peritoneal lymphoid tissues, as selective sites of cancer implantation in peritoneal dissemination. In the present study, we first demonstrated that intraperitoneal injection of adenovirus vector encoding the GFP gene into tumor-free nude mice resulted in GFP expression at omental and mesenteric MS; MS macrophages were target cells for adenovirus infection. We confirmed that intraperitoneal injection of adenovirus vector encoding the NK4 gene (AdNK4) resulted in NK4 production localized to the peritoneal cavity, especially the omentum. Adenovirus vector-mediated MS-selective transgene expression was markedly impaired in tumor-bearing mice whose MS had already been replaced by infiltrating cancer cells. However, prior injection of AdNK4 successfully inhibited MS-selective cancer cell implantation, resulting in suppression of peritoneal dissemination and prolongation of survival. Adenovirus vector-mediated MS-selective delivery of a therapeutic gene may prevent peritoneal dissemination of gastric cancer.