Increased infectivity of adenovirus type 5 bearing type 11 or type 35 fibers to human esophageal and oral carcinoma cells.
Increased infectivity of adenovirus type 5 bearing type 11 or type 35 fibers to human esophageal and oral carcinoma cells.
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DOI：
10.3892/or.14.4.831
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发表时间：
2005-10
期刊：
影响因子：
4.2
通讯作者：
Ling Yu;H. Takenobu;O. Shimozato;K. Kawamura;Y. Nimura;N. Seki;K. Uzawa;H. Tanzawa;H. Shimada;T. Ochiai;M. Tagawa
中科院分区：
文献类型：
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作者：
Ling Yu;H. Takenobu;O. Shimozato;K. Kawamura;Y. Nimura;N. Seki;K. Uzawa;H. Tanzawa;H. Shimada;T. Ochiai;M. Tagawa
食管癌和口腔癌对5型腺病毒（Ad 5）介导的基因转移具有相对抗性，主要是因为Ad 5的细胞受体（柯萨奇病毒和腺病毒受体）的表达在这些类型的肿瘤中通常下调。因此，在肿瘤中受体表达不受抑制的Ad类型是基因转移到肿瘤中的更好载体。CD 46是Ad亚型B2（如Ad 11和Ad 35）的细胞受体，在许多食管和口腔肿瘤细胞中良好表达。由于Ad对靶细胞的感染性主要受其纤维与细胞受体之间的相互作用的影响，我们检测了嵌合Ad 5的感染性，其纤维结构被11型或35型（Ad 5/11或Ad 5/35）所取代，对6个人口腔癌细胞和11个食管癌细胞。我们发现嵌合Ad，特别是Ad 5/35，在所有测试的肿瘤中比Ad 5更有效地感染。然而，Ad 5/35和Ad 5/11介导的转导的功效与靶细胞中Ad亚型B1的细胞受体CD 46或CD 80/86的表达水平无关。这些数据表明，Ad亚型B2是合适的基因转移载体的人上消化道鳞状细胞癌，和Ad亚型B2的感染性可能是由其他受体除了CD 46调节。
Esophageal and oral carcinomas are relatively resistant to adenovirus serotype 5 (Ad5)-mediated gene transfer, primarily because expression of the cellular receptors for Ad5, the coxsackievirus and adenovirus receptor, is often downregulated in these types of tumor. The types of Ad in which the receptor expression is not suppressed in tumors are therefore better vectors for gene transfer into tumors. CD46, a cellular receptor for Ad subtype B2, such as Ad11 and Ad35, is well expressed in a number of esophageal and oral tumor cells. Since the infectivity of Ad to target cells is mainly influenced by the interaction between their fibers and the cellular receptors, we examined the infectivity of chimeric Ad5, whose fiber structure was substituted with that of type 11 or 35 (Ad5/11 or Ad5/35), to 6 human oral and 11 esophagus carcinoma cells. We found that the chimeric Ad, in particular Ad5/35, infected more effectively than Ad5 in all the tumors tested. However, the efficacy of Ad5/35- and Ad5/11-mediated transduction was not correlated with the expression level of CD46 or CD80/86, a cellular receptor of the Ad subtype B1, in the target cells. These data suggest that the Ad subtype B2 are suitable vectors of gene transfer for human squamous cell carcinomas of the upper gastrointestinal tract, and that the infectivity of the Ad subtype B2 can possibly be regulated by other receptors besides CD46.