Interleukin-8 increases VEGF and neuropilin expression and stimulates ERK activation in human pancreatic cancer

• Published in: Cancer science 2008-02, Vol.99 (4), p.733-737
• Main Authors: Li, Min, Zhang, Yuqing, Feurino, Louis W., Wang, Hao, Fisher, William E., Brunicardi, F. Charles, Chen, Changyi, Yao, Qizhi
• Format: Article
• Language: English
• ISSN: 1347-9032; 1349-7006
• DOI: 10.1111/j.1349-7006.2008.00740.x

Interleukin-8 (IL-8) is associated with tumorigenesis by promoting angiogenesis and metastasis. Although upregulation 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 (HPDE) 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 upregulated the expression of VEGF 165 , and 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 ERK1/2 signaling pathway in BxPC-3 cells. Our studies suggest that IL-8 might be a malignant factor in human pancreatic cancer by induction of VEGF and NRP-2 expression and ERK activation. Targeting IL-8 along with other anti-angiogenesis therapy could be an effective treatment for this malignancy.