文章基本信息

标题：SDF-1/54-DCN: A Novel Recombinant Chimera with Dual Inhibitory Effects on Proliferation and Chemotaxis of Tumor Cells
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作者：Weifeng Ma ; Shaoxi Cai ; Jun Du 等
期刊名称：Biological and Pharmaceutical Bulletin
印刷版ISSN：0918-6158
电子版ISSN：1347-5215
出版年度：2008
卷号：31
期号：6
页码：1086-1091
DOI：10.1248/bpb.31.1086
出版社：The Pharmaceutical Society of Japan
摘要：Several studies have shown that the interaction of CXC chemokine receptor 4 (CXCR4) with its ligand, stromal cell-derived factor-1α (SDF-1α) is closely involved in the directional migration of some tumors toward specific organs, which provides a new pathway against cancer metastasis. We previously developed an α-helix-defective mutant of SDF-1α, SDF-1/54 that displays obvious antagonistic activity to CXCR4. But it is necessary to ensure the targeting of SDF-1/54 to tumors in vivo since many normal tissues also express CXCR4. It is known that most tumor cells highly express epidermal growth factor receptor (EGFR). Meanwhile, decorin (DCN), a specific antagonist of EGFR, can target the tumor cells enriched in EGFR and cause a significant downregulation of EGFR. Hereby, we further generated a fusion construct of SDF-1/54 and DCN to expect to enhance the targeting of SDF-1/54 to tumors by dual blocking effects on CXCR4 and EGFR. This study focused on expression of recombinant chimera SDF-1/54-DCN in Escherichia coli , purification and bioactivity to inhibit the physiological functions mediated by CXCR4 and EGFR respectively in various tumor cell lines in vitro . Results indicated that SDF-1/54-DCN could inhibit both chemotaxis and proliferation of the tumor cells we used, which may be attributed to its blocking to CXCR4 and EGFR. These findings suggest that this strategy to link SDF-1/54 with DCN may be a promising approach to increase the targeting of SDF-1/54 to the tumors coexpressing CXCR4 and EGFR.
关键词：stromal cell-derived factor-1α;decorin;chimera;chemotaxis;proliferation