Vascular and Biology 02

• Published in: British journal of surgery Vol. 89; no. S1; p. 40
• Main Authors: Dowsland, M.H., Ali, S.A., Kirby, J.A., Lennard, T.W.J.
• Format: Journal Article
• Language: English
• Published: Chichester, UK John Wiley & Sons, Ltd 2002
• ISSN: 0007-1323; 1365-2168
• DOI: 10.1046/j.1365-2168.89.s.1.28_2.x

Background: The chemokine receptor CXCR4 is linked to chemokine‐mediated metastasis in breast cancer. The breast cancer microenvironment is rich in cytokines, known to have a regulatory effect on CXCR4. We examined the inflammatory cytokine regulation of CXCR4 surface expression and its effect on migration in MCF‐7 and MDA MB231 cells. As heparin competitively antagonizes chemokines we evaluated its potential to block migration of these cell lines towards the chemokine SDF‐1.
Methods: Expression of CXCR4 was analysed by flow cytometry (R & D Mab 172) before and after stimulation with TNF‐α or IFN‐γ. The effects of TNF‐α and heparin on migration were examined by chemotaxis assays.
Results: TNF‐α significantly reduced CXCR4 expression in both cell lines after 24 h (MCF‐7: 83 per cent*; MDA MB231: 89 per cent*). In MCF‐7 cells IFN‐γ reduced expression (97 per cent*) by 24 h; a bi‐phasic response was observed for MDA MB 231 cells, with a maximal reduction occurring after 16 h (83 per cent*), returning to unstimulated levels by 24 h. The reduction in CXCR4 expression by TNF‐α was consistent with reduced migration towards SDF‐1 (MCF‐7 by 80 per cent*, MDA MB231 by 94 per cent*). Heparin also inhibited chemotaxis of MCF‐7 (at 250 µg mL−1*) and MDA MB231 (at 100 µg mL−1 and 250 µg mL−1*).
Conclusions: Regulation of the CXCR4 by proinflammatory cytokines alters the ability of breast cancer cells to migrate towards SDF‐1. Heparin significantly reduces SDF‐1 induced breast cancer cell migration, suggesting a potential therapeutic action in patients with breast cancer.
Statistics: Student's one‐tailed t‐test. (*P < 0.05) (TNF‐α: tumour necrosis factor alpha, IFN‐γ: interferon gamma, SDF‐1: stromal derived factor‐1)