Marine Lectins DlFBL and HddSBL Fused with Soluble Coxsackie-Adenovirus Receptor Facilitate Adenovirus Infection in Cancer Cells BUT Have Different Effects on Cell Survival.
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 labraxfucose binding lectin (DlFBL) andHaliotis discus discussialic 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 encodingPinellia pedatisectaagglutinin (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.
College of Life Sciences, Zhejiang Sci-Tech University, Hangzhou 310018, Zhejiang, China. 13803669864@163.com.
Bingbing
B
Wu
College of Life Sciences, Zhejiang Sci-Tech University, Hangzhou 310018, Zhejiang, China. mss1053280369@163.com.
Shengsheng
S
Mei
College of Life Sciences, Zhejiang Sci-Tech University, Hangzhou 310018, Zhejiang, China. clz_2016@yeah.net.
Lianzhen
L
Cui
College of Life Sciences, Zhejiang Sci-Tech University, Hangzhou 310018, Zhejiang, China. 17826855065@163.com.
Zhenzhen
Z
Zhao
College of Life Sciences, Zhejiang Sci-Tech University, Hangzhou 310018, Zhejiang, China. cjh15067149909@163.com.
Jianhong
J
Chen
College of Life Sciences, Zhejiang Sci-Tech University, Hangzhou 310018, Zhejiang, China. wutao0920@163.com.
Tao
T
Wu
College of Life Sciences, Zhejiang Sci-Tech University, Hangzhou 310018, Zhejiang, China. lgc@zstu.edu.cn.
Gongchu
G
Li
D000256:Adenoviridae / Q000235:genetics*; D000257:Adenoviridae Infections / Q000235:genetics*; D017209:Apoptosis / Q000235:genetics; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000235:genetics*; D062727:Coxsackie and Adenovirus Receptor-Like Membrane Protein / Q000235:genetics*; D050687:E2F1 Transcription Factor / Q000235:genetics; D015316:Genetic Therapy / Q000379:methods; D005822:Genetic Vectors / Q000235:genetics; D006801:Humans; D020014:K562 Cells; D037102:Lectins / Q000235:genetics*; D009369:Neoplasms / Q000628:therapy*; D015398:Signal Transduction / Q000235:genetics
D062727:Coxsackie and Adenovirus Receptor-Like Membrane Protein; D050687:E2F1 Transcription Factor; D037102:Lectins; C027112:fucose-binding lectin
DlFBL; E2F1; HddSBL; adenovirus