Marine Lectins DlFBL and HddSBL Fused with Soluble Coxsackie-Adenovirus Receptor Facilitate Adenovirus Infection in Cancer Cells BUT Have Different Effects on Cell Survival

Bingbing Wu,Shengsheng Mei,Jianhong Chen,Zhenzhen Zhao,Lianzhen Cui,Tao Wu,Gongchu Li

doi:10.3390/md15030073

Abstract

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.

Highlights

Lectins, carbohydrate-binding proteins that bind reversibly with mono- or oligosaccharides, have been extensively studied in basic and clinical cancer research, and have shown potential prognostic, diagnostic, and therapeutic values
Further analysis revealed that soluble coxsackie-adenovirus receptor (sCAR)-Haliotis discus discus sialic acid binding lectin (HddSBL), but not sCAR-Dicentrarchus labrax fucose binding lectin (DlFBL), significantly upregulated transcription factor E2F1 levels in U87MG cells, which might be responsible for the adverse effect of sCAR-HddSBL on Ad-Pinellia pedatisecta agglutinin (PPA) and Ad-DlFBL
Recombinant sCAR-DlFBL and sCAR-HddSBL produced in a bacterial expression system successfully facilitated Ad-EGFP infection in K562/ADR and U87MG cells

Summary

Introduction

Carbohydrate-binding proteins that bind reversibly with mono- or oligosaccharides, have been extensively studied in basic and clinical cancer research, and have shown potential prognostic, diagnostic, and therapeutic values. Lectins have shown potential values for developing therapeutic agents for various cancers. A [2], Fenneropenaeus indicus hemolymph fucose binding lectin [3], Polygonatum cyrtonema lectin [4], as well as MytiLec [5,6,7] were shown to be cytotoxic to various cancer cells through inducing apoptosis or autophagy. Pinellia pedatisecta agglutinin (PPA), as well as marine lectins, such as galectin Anguilla japonica lectin 1, Haliotis discus discus sialic acid binding lectin (HddSBL), Dicentrarchus labrax fucose binding lectin (DlFBL), and Strongylocentrotus purpuratus rhamnose binding lectin, could be exogenously expressed in various cancer cells and led to cancer cell death [8,9,10,11].

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