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

Abstract

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(165), 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.

• Authors: Min Li, Yuqing Zhang, Louis W Feurino, Hao Wang, William E Fisher, F Charles Brunicardi, Changyi Chen, Qizhi Yao
• Journal: Cancer science (Cancer Sci) Vol. 99 Issue 4 Pg. 733-7 (Apr 2008) ISSN: 1349-7006 [Electronic] England
• PMID: 18307536 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Interleukin-8
• Neuropilin-2
• Vascular Endothelial Growth Factor A
• Cobalt
• Extracellular Signal-Regulated MAP Kinases
• cobaltous chloride

Topics

• Cell Hypoxia
• Cell Line, Tumor
• Cobalt (toxicity)
• Extracellular Signal-Regulated MAP Kinases (genetics, metabolism)
• Humans
• Interleukin-8 (genetics, metabolism)
• Neovascularization, Pathologic (genetics, metabolism)
• Neuropilin-2 (genetics, metabolism)
• Pancreatic Neoplasms (blood supply, enzymology, metabolism)
• Up-Regulation
• Vascular Endothelial Growth Factor A (genetics, metabolism)