Marine Lectins DlFBL and HddSBL Fused with Soluble Coxsackie-Adenovirus Receptor Facilitate Adenovirus Infection in Cancer Cells BUT Have Different Effects on Cell Survival.
Marine Lectins DlFBL and HddSBL Fused with Soluble Coxsackie-Adenovirus Receptor Facilitate Adenovirus Infection in Cancer Cells BUT Have Different Effects on Cell Survival.
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海洋凝集素 DlFBL 和 HddSBL 与可溶性柯萨奇腺病毒受体融合促进癌细胞中的腺病毒感染，但对细胞存活有不同的影响
DOI：
10.3390/md15030073
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发表时间：
2017-03-14
期刊：
影响因子：
5.4
通讯作者：
Li G
中科院分区：
文献类型：
--
作者：
Wu B;Mei S;Cui L;Zhao Z;Chen J;Wu T;Li G
癌症的发展和进展通常与糖基化变化相关，为各种癌症提供预后和诊断生物标志物以及治疗靶点。本工作将皱纹盘鲍岩藻糖结合凝集素（DlFBL）和皱纹盘鲍唾液酸结合凝集素（HddSBL）与可溶性柯萨奇-腺病毒受体（sCAR）基因融合，并通过细菌表达系统表达。结果表明，重组sCAR-DlFBL不仅能促进腺病毒Ad-EGFP感染K562/ADR和U87 MG细胞，而且能增强携带掌叶半夏凝集素（PPA）或DlFBL基因的腺病毒（Ad-PPA或Ad-DlFBL）对U87 MG细胞的杀伤作用，诱导细胞凋亡。重组sCAR-HddSBL促进Ad-EGFP感染，但显著抵消Ad-PPA和Ad-DlFBL在U87 MG细胞中的细胞毒性。进一步分析显示，sCAR-HddSBL而不是sCAR-DlFBL显著上调U87 MG细胞中转录因子E2 F1的水平，这可能是sCAR-HddSBL对Ad-PPA和Ad-DlFBL的不利影响的原因。综上所述，我们的数据表明，sCAR-DIFBL可以进一步开发以重定向治疗性腺病毒以感染癌细胞如U87 MG，并且用于腺病毒重定向的sCAR-凝集素融合蛋白应该仔细检查凝集素如HddSBL诱导的可能的存活信号传导。
Cancer development and progression are usually associated with glycosylation change, providing prognostic and diagnostic biomarkers, as well as therapeutic targets, for various cancers. In this work, Dicentrarchus labrax fucose binding lectin (DlFBL) and Haliotis discus discus sialic acid binding lectin (HddSBL) were genetically fused with soluble coxsackie-adenovirus receptor (sCAR), and produced through a bacterial expression system. Results showed that recombinant sCAR-DlFBL not only facilitated adenovirus Ad-EGFP infection in K562/ADR and U87MG cells, but also enhanced the cytotoxicity of adenovirus harboring gene encoding Pinellia pedatisecta agglutinin (PPA) or DlFBL (Ad-PPA or Ad-DlFBL) on U87MG cells through inducing apoptosis. Recombinant sCAR-HddSBL facilitated Ad-EGFP infection, but dramatically counteracted the cytotoxicity of both Ad-PPA and Ad-DlFBL in U87MG cells. Further analysis revealed that sCAR-HddSBL, but not sCAR-DlFBL, significantly upregulated transcription factor E2F1 levels in U87MG cells, which might be responsible for the adverse effect of sCAR-HddSBL on Ad-PPA and Ad-DlFBL. Taken together, our data suggested that sCAR-DlFBL could be further developed to redirect therapeutic adenoviruses to infect cancer cells such as U87MG, and the sCAR-lectin fusion proteins for adenoviral retargeting should be carefully examined for possible survival signaling induced by lectins, such as HddSBL.