The correlation of IL-8 signaling pathway and EGFR pathway in MDA-231 cells of breast carcinoma

Objective: To study the effect of IL-8 on cell proliferation and invasion, and to analyze the correlations between chemokine and epidermal growth factor receptor (EGFR) signaling pathways in breast carcinoma cells. Methods: IL-8 secretion responded to treatment with rhEGF and anti-EGFR and expression of its receptors CXCR1, CXCR2 in MDA-231 cells were measured by ELISA and immunocytochem-istry, respectively. Effect of rhIL-8 and neutralizing antibody on cell proliferation and invasion were analyzed by using MTT and matrigel invasion assay. EGFR transactivation stimulated with rhIL-8 and neutralizing antibody was assessed by Western blot using anti-phosphotyrosine antibody. Results: MDA-231. cells released high level of IL-8 and two receptors of IL-8 (CXCR1 and CXCR2) both expressed on cell membrane. Exogenous IL-8 and its neutralizing antibody did not significantly influence the proliferation of breast carcinoma cells, but rhIL-8 stimulated invasive activity in MDA-231 cells and its neutralizing antibody inhibited the invasive activity (P<0.05). EGF and anti-EGFR both inhibited the secretion of IL-8 in breast carcinoma cells, and IL-8 had no effect on EGFR phosphorylation, but anti-IL-8 induced transactivation of EGFR after 24 h. Conclusion: IL-8 contributes to tumor progression in breast carcinoma through its enhancement of invasive activity but not act as an autocrine growth factor. The correlation of competitive inhibition rather than cross-talk is found between G protein coupled receptor (GPCR)-mediated IL-8 signaling pathway and EGFR pathway in breast carcinoma.