IL-6 stimulates Th2 type cytokine secretion and upregulates VEGF and NRP-1 expression in pancreatic cancer cells

Abstract

BACKGROUND. Although upregulation of interleukin-6 (IL-6) is associated with many solid tumors, its role in pancreatic cancer has not been well elucidated. In this study, we examined the expression of IL-6 in pancreatic cancer cells, and determined the effect of exogenous IL-6 on cytokine secretion, gene expression, and signaling in human pancreatic cancer cells. METHODS. The mRNA levels of IL-6, VEGF165, neuropilin-1 (NRP-1), and neuropilin-2 (NRP-2) were determined by real-time RT PCR. Phosphorylation of ERK2 in pancreatic cancer cells was determined by using Bio-Plex phosphoprotein assay. The expression of IL-6 and other cytokines in human pancreatic cancer cell lines was determined with Bio-Plex cytokine assay. RESULTS. Pancreatic cancer cell lines expressed higher levels of IL-6 than normal human pancreatic ductal epithelium (HPDE) cells. Exogenous IL-6 increased the secretion of multiple Th2 type of cytokines in Panc-1, MIA PaCa-2, and BxPC-3 cells. IL-6 also upregulated the expression of VEGF165, and NRP-1, and both IL-6 and VEGF165 were inducible by hypoxia. In addition, IL-6 activated ERK2 signaling pathways in pancreatic cancer cells. CONCLUSIONS. IL-6 may be involved in promoting human pancreatic cancer development by furnishing Th2 type of cytokine environment and upregulating cell proliferation and angiogenesis related genes. Targeting IL-6 might be an effective treatment for pancreatic cancer.