TNFα-activated stromal COX-2 signalling promotes proliferative and invasive potential of colon cancer epithelial cells

M. Zhu, Y. Zhu, Michael P Lance

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Objectives: Up to now it has been unclear whether stromal/epithelial interaction affects progression of colon cancer. This study was designed to examine effects of tumour necrosis factor alpha (TNFα)-activated stromal cyclooxygenase-2 (COX-2) signalling on proliferation and invasiveness of colon cancer epithelial cells. Materials and methods: Cyclooxygenase-2 mRNA and protein were determined by real-time PCR and western blotting and prostaglandin E2 (PGE2) was assayed by radioimmunoassay. Cell proliferation and invasiveness were determined by transwell chamber assays and protein kinase C (PKC) was assayed by Biotrak PKC Assay System. Results: Our results indicated that TNFα, a powerful inflammatory cytokine, strongly promoted COX-2 expression and PGE2 production in colon cancer-associated fibroblasts. Using in vitro assays for estimating proliferative and invasive potential, we discovered that activation of stromal COX-2 signalling significantly promoted proliferation and invasiveness of colon cancer epithelial cells. In addition, selective COX-2 inhibitor N-[2-(Cyclohexyloxy)-4-nitrophenyl]methanesulfonamide, blocked such proliferative and invasive effects on the cancer epithelial cells. In this process, PKC was involved in activation of COX-2 signalling in the fibroblasts. Conclusion: We conclude that activation of stromal COX-2 signalling by TNFα played a major role in promoting proliferation and invasiveness of colon cancer epithelial cells.

Original languageEnglish (US)
Pages (from-to)374-381
Number of pages8
JournalCell Proliferation
Volume46
Issue number4
DOIs
StatePublished - Aug 2013

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Cyclooxygenase 2
Colonic Neoplasms
Tumor Necrosis Factor-alpha
Epithelial Cells
Protein Kinase C
Dinoprostone
Cyclooxygenase 2 Inhibitors
Radioimmunoassay
Real-Time Polymerase Chain Reaction
Fibroblasts
Western Blotting
Cell Proliferation
Cytokines
Messenger RNA
Neoplasms
Proteins

ASJC Scopus subject areas

  • Cell Biology

Cite this

TNFα-activated stromal COX-2 signalling promotes proliferative and invasive potential of colon cancer epithelial cells. / Zhu, M.; Zhu, Y.; Lance, Michael P.

In: Cell Proliferation, Vol. 46, No. 4, 08.2013, p. 374-381.

Research output: Contribution to journalArticle

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abstract = "Objectives: Up to now it has been unclear whether stromal/epithelial interaction affects progression of colon cancer. This study was designed to examine effects of tumour necrosis factor alpha (TNFα)-activated stromal cyclooxygenase-2 (COX-2) signalling on proliferation and invasiveness of colon cancer epithelial cells. Materials and methods: Cyclooxygenase-2 mRNA and protein were determined by real-time PCR and western blotting and prostaglandin E2 (PGE2) was assayed by radioimmunoassay. Cell proliferation and invasiveness were determined by transwell chamber assays and protein kinase C (PKC) was assayed by Biotrak™ PKC Assay System. Results: Our results indicated that TNFα, a powerful inflammatory cytokine, strongly promoted COX-2 expression and PGE2 production in colon cancer-associated fibroblasts. Using in vitro assays for estimating proliferative and invasive potential, we discovered that activation of stromal COX-2 signalling significantly promoted proliferation and invasiveness of colon cancer epithelial cells. In addition, selective COX-2 inhibitor N-[2-(Cyclohexyloxy)-4-nitrophenyl]methanesulfonamide, blocked such proliferative and invasive effects on the cancer epithelial cells. In this process, PKC was involved in activation of COX-2 signalling in the fibroblasts. Conclusion: We conclude that activation of stromal COX-2 signalling by TNFα played a major role in promoting proliferation and invasiveness of colon cancer epithelial cells.",
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