Signal of proteinase-activated receptor-2 contributes to highly malignant potential of human pancreatic cancer by up-regulation of interleukin-8 release

  • Authors:
    • Osamu Ikeda
    • Hiroshi Egami
    • Takatoshi Ishiko
    • Shinji Ishikawa
    • Hidenobu Kamohara
    • Hideki Hidaka
    • Masahumi Takahashi
    • Michio Ogawa
  • View Affiliations

  • Published online on: April 1, 2006     https://doi.org/10.3892/ijo.28.4.939
  • Pages: 939-946
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Abstract

Proteinase-activated receptor-2 (PAR-2) is expressed in various tissues, including cancer lesions. However, the functional consequences of PAR-2 expression in cancer cells, especially in pancreatic cancer cells, are poorly understood. To clarify the biological significance of PAR-2 signaling in pancreatic cancer, we examined the production of growth factors and cytokines, such as IL-6, IL-8, bFGF, TGF-β1, and VEGF, by specific ELISAs. Two human pancreatic cancer cell lines, SUIT2 and MiaPaCa2, which have been shown to express PAR-2, were stimulated by trypsin and PAR-2 activating peptide (PAR-2AP: SLIGKV-NH2). After 24 h, the culture supernatants were collected and specific ELISAs were performed. Although no significant changes were observed in the release of IL-6, bFGF, TGF-β1, or VEGF, that of IL-8 was significantly up-regulated by PAR-2 agonists in a dose-dependent manner. In addition, IL-8 receptor expression was found in pancreatic cancer cells and fibroblasts. These results suggest that the PAR-2 signal up-regulates IL-8 release from pancreatic cancer cells. This up-regulated IL-8 has an effect on the pancreatic cancer cells in an autocrine manner and on the fibroblasts in a paracrine manner. Thus, this signal might contribute to tumor progression and characteristic fibrosis in pancreatic cancer.

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April 2006
Volume 28 Issue 4

Print ISSN: 1019-6439
Online ISSN:1791-2423

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APA
Ikeda, O., Egami, H., Ishiko, T., Ishikawa, S., Kamohara, H., Hidaka, H. ... Ogawa, M. (2006). Signal of proteinase-activated receptor-2 contributes to highly malignant potential of human pancreatic cancer by up-regulation of interleukin-8 release. International Journal of Oncology, 28, 939-946. https://doi.org/10.3892/ijo.28.4.939
MLA
Ikeda, O., Egami, H., Ishiko, T., Ishikawa, S., Kamohara, H., Hidaka, H., Takahashi, M., Ogawa, M."Signal of proteinase-activated receptor-2 contributes to highly malignant potential of human pancreatic cancer by up-regulation of interleukin-8 release". International Journal of Oncology 28.4 (2006): 939-946.
Chicago
Ikeda, O., Egami, H., Ishiko, T., Ishikawa, S., Kamohara, H., Hidaka, H., Takahashi, M., Ogawa, M."Signal of proteinase-activated receptor-2 contributes to highly malignant potential of human pancreatic cancer by up-regulation of interleukin-8 release". International Journal of Oncology 28, no. 4 (2006): 939-946. https://doi.org/10.3892/ijo.28.4.939