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

Cancer Biol Ther. 2007 Jul;6(7):1096-100. doi: 10.4161/cbt.6.7.4328.


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 develop ment 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cytokines / biosynthesis*
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Gene Expression Regulation, Neoplastic / drug effects*
  • Humans
  • Interleukin-6 / genetics
  • Interleukin-6 / pharmacology*
  • MAP Kinase Signaling System / drug effects
  • Neuropilin-1 / genetics*
  • Pancreatic Neoplasms / blood supply
  • Pancreatic Neoplasms / etiology*
  • Pancreatic Neoplasms / immunology
  • Pancreatic Neoplasms / pathology
  • RNA, Messenger / analysis
  • Th2 Cells / drug effects*
  • Th2 Cells / immunology
  • Up-Regulation
  • Vascular Endothelial Growth Factor A / genetics*


  • Cytokines
  • Interleukin-6
  • RNA, Messenger
  • Vascular Endothelial Growth Factor A
  • Neuropilin-1
  • Extracellular Signal-Regulated MAP Kinases