Potential involvement of IL-8 and its receptors in the invasiveness of pancreatic cancer cells

Int J Oncol. 2003 Apr;22(4):765-71.


The purpose of the present study was to examine the expression of interleukin (IL)-8 and IL-8 receptors and to evaluate the effects of IL-8 on human pancreatic cancer. We examined the expression of IL-8 and its two receptors (CXCR1 and CXCR2) in 40 surgically resected human pancreatic cancer tissues and in three different human pancreatic cancer cell lines (PANC-1, MIAPaCa-2 and Capan-2). The immunohistochemical analysis using specific antibodies demonstrated that positive staining for IL-8, CXCR1 and CXCR2 in surgically resected human pancreatic cancer was 50, 55 and 65%, respectively. Moreover, 40% of these cases were positive for both IL-8 and IL-8 receptors. In contrast, immunoreactive signals for those proteins were extremely suppressed in normal pancreatic tissues. All of the pancreatic cancer cell lines expressed IL-8 and IL-8 receptors at the RNA and protein levels. Receptor binding experiments using 125I-labeled IL-8 showed that PANC-1 cells had specific binding sites for IL-8. The cell proliferation assay demonstrated that IL-8 did not affect the growth of the three cell lines. However, treatment with IL-8 enhanced the invasiveness into Matrigel and increased the activity of matrix metalloproteinase (MMP)-2 in supernatants of the PANC-1 cells. These results demonstrate that IL-8 and IL-8 receptors are over-expressed in pancreatic cancer, and suggest that IL-8 regulates MMP-2 activity and plays an important role in the invasiveness of human pancreatic cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding Sites
  • Blotting, Western
  • Cell Division
  • Cell Line, Tumor
  • Dose-Response Relationship, Drug
  • Gelatin / pharmacology
  • Humans
  • Immunohistochemistry
  • Interleukin-8 / metabolism
  • Interleukin-8 / physiology*
  • Matrix Metalloproteinase 2 / metabolism*
  • Neoplasm Invasiveness
  • Pancreatic Neoplasms / metabolism*
  • Pancreatic Neoplasms / pathology*
  • Precipitin Tests
  • Protein Binding
  • RNA / metabolism
  • Receptors, Interleukin-8A / metabolism
  • Receptors, Interleukin-8A / physiology*
  • Receptors, Interleukin-8B / metabolism
  • Receptors, Interleukin-8B / physiology*
  • Recombinant Proteins / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction


  • Interleukin-8
  • Receptors, Interleukin-8A
  • Receptors, Interleukin-8B
  • Recombinant Proteins
  • RNA
  • Gelatin
  • Matrix Metalloproteinase 2