Interleukin‐8 increases vascular endothelial growth factor and neuropilin expression and stimulates ERK activation in human pancreatic cancer

<jats:p>Interleukin‐8 (IL‐8) is associated with tumorigenesis by promoting angiogenesis and metastasis. Although up‐regulation of IL‐8 is indicated in many cancers, its function in pancreatic cancer has not been well characterized. In this study we examined the expression of IL‐8 on pancreatic cancer cells and clinical tissue specimens, and investigated the effect of exogenous IL‐8 on gene expression, and signaling in human pancreatic cancer cells. We found that pancreatic cancer cells expressed higher amount of IL‐8 mRNA than normal human pancreatic ductal epithelium cells. IL‐8 mRNA was also substantially overexpressed in 11 of 14 (79%) clinical pancreatic‐adenocarcinoma samples compared with that in their surrounding normal tissues. Exogenous IL‐8 up‐regulated the expression of vascular endothelial growth factor<jats:sub>165</jats:sub>, and neuropilin (NRP)‐2 in BxPC‐3 cells, one of human pancreatic cancer cell lines. IL‐8 expression was inducible by hypoxia mimicking reagent cobalt chloride. In addition, IL‐8 activated extracellular signal‐regulated kinase (ERK)1/2 signaling pathway in BxPC‐3 cells. Our studies suggest that IL‐8 might be a malignant factor in human pancreatic cancer by induction of vascular endothelial growth factor and NRP‐2 expression and ERK activation. Targeting IL‐8 along with other antiangiogenesis therapy could be an effective treatment for this malignancy. (<jats:italic>Cancer Sci</jats:italic> 2008, 99: 733–737)</jats:p>