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

Abstract

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.

• Authors: Yukio Kuwada, Tamito Sasaki, Kenji Morinaka, Yasuhiko Kitadai, Naofumi Mukaida, Kazuaki Chayama
• Journal: International journal of oncology (Int J Oncol) Vol. 22 Issue 4 Pg. 765-71 (Apr 2003) ISSN: 1019-6439 [Print] Greece
• PMID: 12632066 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

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