Abstract
Abstract Introduction: The CXCL7/CXCR2 axis interfaces with matrix molecules whereby the chemokine CXCL7 binds heparan sulfate and the G-protein-linked receptor CXCR2. CXCL7-transfected breast cells acquire the ability to invade through Matrigel. The purpose of this study was to test the effect of inhibition of heparan sulfate binding and CXCR2 binding on invasion. Methods: Stably transfected breast cells (MCF10AT) were tested with CXCL7-siRNA, and a specific CXCR2 antagonist (SB225002). Inhibition was verified by real time PCR and heparanase ELISA assay. Matrigel invasion assays were performed. Results: SB225002 and CXCL7 siRNA blocked invasion through Matrigel as compared to controls (p<0.01), and CXCL7 siRNA significantly decreased heparanase activity (p<0.01). Conclusion: Interfering with either heparan sulfate binding by CXCL7 or its binding to CXCR2 leads to decreased invasion through Matrigel. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5276.
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