Interleukin-8 increases vascular endothelial growth factor and neuropilin expression and stimulates ERK activation in human pancreatic cancer.
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.
Li
Min
M
Molecular Surgeon Research Center, Elkins Pancreas Center, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, Texas 77030, USA. minli@bcm.edu
Zhang
Yuqing
Y
Feurino
Louis W
LW
Wang
Hao
H
Fisher
William E
WE
Brunicardi
F Charles
FC
Chen
Changyi
C
Yao
Qizhi
Q
D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D003035:Cobalt / Q000633:toxicity; D048049:Extracellular Signal-Regulated MAP Kinases / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism*; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000378:metabolism*; D039943:Neuropilin-2 / Q000235:genetics / Q000378:metabolism*; D010190:Pancreatic Neoplasms / Q000098:blood supply* / Q000201:enzymology / Q000378:metabolism*; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism*
D016209:Interleukin-8; D039943:Neuropilin-2; D042461:Vascular Endothelial Growth Factor A; D003035:Cobalt; D048049:Extracellular Signal-Regulated MAP Kinases; C018021:cobaltous chloride