Adenoviral transduction of MRP-1/CD9 and KAI1/CD82 inhibits lymph node metastasis in orthotopic lung cancer model.
Adenoviral transduction of MRP-1/CD9 and KAI1/CD82 inhibits lymph node metastasis in orthotopic lung cancer model.
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DOI：
10.1158/0008-5472.can-06-3090
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发表时间：
2007-02
期刊：
影响因子：
11.2
通讯作者：
Takayuki Takeda;N. Hattori;T. Tokuhara;Y. Nishimura;M. Yokoyama;M. Miyake
中科院分区：
文献类型：
--
作者：
Takayuki Takeda;N. Hattori;T. Tokuhara;Y. Nishimura;M. Yokoyama;M. Miyake
传统的治疗方法对肺癌转移的疗效仍然较差，因此导致这种疾病的预后很差。虽然肿瘤转移的过程还不清楚，但我们以前的研究表明，癌细胞中MRP-1/CD9和KAI1/CD82的高表达水平与低转移潜能显著相关。为了确定将这些Tetraspanins基因转移到肺肿瘤细胞是否可能是调节转移的有用策略，我们采用了Lewis肺癌(LLC)细胞肺内种植造成的原位肺癌模型，并使用两种不同的基因传递方法评估了LLC细胞在纵隔淋巴结中的转移生长：(A)将预先感染了编码MRP-1/CD9基因、KAI1/CD82基因或LacZ基因的腺病毒的LLC细胞植入小鼠肺内；(B)将这些腺病毒注入原位植入LLC细胞的小鼠气管内。在这两种情况下，我们发现，与LacZ基因相比，MRP-1/CD9或KAI1/CD82基因转移显著减少了纵隔淋巴结的转移，而不影响种植部位的原发肿瘤生长。这些结果再次强调了MRP-1/CD9和KAI1/CD82在抑制转移过程中的重要作用，也表明了使用这些Tetraspanins对肺癌进行基因治疗以防止区域淋巴结转移的可行性。因此，这一策略可能在临床上作为一种预防治疗来抑制淋巴结转移的发生。
Conventional therapies still remain less effective for metastasis of lung cancer, thus leading to a poor prognosis for this disorder. Although the processes involved in metastasis have not yet been clearly elucidated, our previous studies have shown that higher expression levels of MRP-1/CD9 and KAI1/CD82 in cancer cells are significantly correlated with less metastatic potency. To determine whether the gene transfer of these tetraspanins into lung tumor cells may be a useful strategy to regulate metastasis, we adopted an orthotopic lung cancer model produced by the intrapulmonary implantation of Lewis lung carcinoma (LLC) cells and evaluated the metastatic growth in the mediastinal lymph nodes using two different methods of gene delivery as follows: (a) the implantation of LLC cells preinfected with adenovirus encoding either MRP-1/CD9 cDNA, KAI1/CD82 cDNA, or LacZ gene into the mouse lung and (b) the intratracheal administration of these adenoviruses into the mice orthotopically preimplanted with LLC cells. In both cases, we found that the delivery of either MRP-1/CD9 or KAI1/CD82 cDNA dramatically reduced the metastases to the mediastinal lymph nodes in comparison with those of LacZ gene delivery, without affecting the primary tumor growth at the implanted site. These results reemphasize the important role of MRP-1/CD9 and KAI1/CD82 in the suppression of the metastatic process and also show the feasibility of gene therapy when using these tetraspanins for lung cancer to prevent metastasis to the regional lymph nodes. This strategy may therefore be clinically applicable as a prophylactic treatment to suppress the occurrence of lymph node metastasis.