IL1Β-mediated Stromal COX-2 signaling mediates proliferation and invasiveness of colonic epithelial cancer cells

Yingting Zhu, Min Zhu, Peter Lance

Research output: Contribution to journalArticle

24 Scopus citations

Abstract

COX-2 is a major inflammatory mediator implicated in colorectal inflammation and cancer. However, the exact origin and role of COX-2 on colorectal inflammation and carcinogenesis are still not well defined. Recently, we reported that COX-2 and iNOS signalings interact in colonic CCD18Co fibroblasts. In this article, we investigated whether activation of COX-2 signaling by IL1Β in primary colonic fibroblasts obtained from normal and cancer patients play a critical role in regulation of proliferation and invasiveness of human colonic epithelial cancer cells. Our results demonstrated that COX-2 level was significantly higher in cancer associated fibroblasts than that in normal fibroblasts with or without stimulation of IL-1Β, a powerful stimulator of COX-2. Using in vitro assays for estimating proliferative and invasive potential, we discovered that the proliferation and invasiveness of the epithelial cancer cells were much greater when the cells were co-cultured with cancer associated fibroblasts than with normal fibroblasts, with or without stimulation of IL1Β. Further analysis indicated that the major COX-2 product, prostaglandin E2, directly enhanced proliferation and invasiveness of the epithelial cancer cells in the absence of fibroblasts. Moreover, a selective COX-2 inhibitor, NS-398, blocked the proliferative and invasive effect of both normal and cancer associate fibroblasts on the epithelial cancer cells, with or without stimulation of IL-1Β. Those results indicate that activation of COX-2 signaling in the fibroblasts plays a major role in promoting proliferation and invasiveness of the epithelial cancer cells. In this process, PKC is involved in the activation of COX-2 signaling induced by IL-1Β in the fibroblasts.

Original languageEnglish (US)
Pages (from-to)2520-2530
Number of pages11
JournalExperimental Cell Research
Volume318
Issue number19
DOIs
StatePublished - Nov 15 2012

Keywords

  • Cancer
  • Colonic fibroblasts
  • Cyclooxygenase-2
  • Interleukin 1-Β
  • Invasion
  • Proliferation
  • Protein kinase C

ASJC Scopus subject areas

  • Cell Biology

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