SDF-1/54-DCN: a novel recombinant chimera with dual inhibitory effects on proliferation and chemotaxis of tumor cells.

Abstract

Several studies have shown that the interaction of CXC chemokine receptor 4 (CXCR4) with its ligand, stromal cell-derived factor-1alpha (SDF-1alpha) 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 alpha-helix-defective mutant of SDF-1alpha, 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.

• Authors: Weifeng Ma, Shaoxi Cai, Jun Du, Yi Tan, Hongyuan Chen, Zhigang Guo, Houwen Hu, Rui Fang, Shaohui Cai
• Journal: Biological & pharmaceutical bulletin (Biol Pharm Bull) Vol. 31 Issue 6 Pg. 1086-91 (Jun 2008) ISSN: 0918-6158 [Print] Japan
• PMID: 18520035 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• CXCL12 protein, human
• Chemokine CXCL12
• Immunotoxins
• Receptors, CXCR4
• ErbB Receptors

Topics

• Antineoplastic Agents (isolation & purification, pharmacology)
• Blotting, Western
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Chemokine CXCL12 (genetics, pharmacology)
• Chemotaxis (drug effects)
• ErbB Receptors (metabolism)
• Escherichia coli (metabolism)
• Humans
• Immunotoxins (isolation & purification, pharmacology)
• Plasmids (genetics)
• Protein Renaturation
• Receptors, CXCR4 (metabolism)