Potential involvement of IL-8 and its receptors in the invasiveness of pancreatic cancer cells.
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.
Kuwada
Yukio
Y
Department of Medicine and Molecular Science, Hiroshima University Graduate School of Biomedical Sciences, Hiroshima 734-8551, Japan. ykuwada@hiroshima-u.ac.jp
Sasaki
Tamito
T
Morinaka
Kenji
K
Kitadai
Yasuhiko
Y
Mukaida
Naofumi
N
Chayama
Kazuaki
K
D001665:Binding Sites; D015153:Blotting, Western; D002455:Cell Division; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D005780:Gelatin / Q000494:pharmacology; D006801:Humans; D007150:Immunohistochemistry; D016209:Interleukin-8 / Q000378:metabolism / Q000502:physiology*; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000473:pathology*; D011233:Precipitin Tests; D011485:Protein Binding; D012313:RNA / Q000378:metabolism; D023062:Receptors, Interleukin-8A / Q000378:metabolism / Q000502:physiology*; D023063:Receptors, Interleukin-8B / Q000378:metabolism / Q000502:physiology*; D011994:Recombinant Proteins / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
D016209:Interleukin-8; D023062:Receptors, Interleukin-8A; D023063:Receptors, Interleukin-8B; D011994:Recombinant Proteins; D012313:RNA; D005780:Gelatin; D020778:Matrix Metalloproteinase 2