Endogenous PGE2 induces MCP‑1 expression via EP4/p38 MAPK signaling in melanoma

Tang,Mingrui; Wang,Yuxin; Han,Sihuan; Guo,Shu; Xu,Nan; Guo,Jiayan

doi:10.3892/ol.2012.1047

Endogenous PGE2 induces MCP‑1 expression via EP4/p38 MAPK signaling in melanoma

Authors:
- Mingrui Tang
- Yuxin Wang
- Sihuan Han
- Shu Guo
- Nan Xu
- Jiayan Guo
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Affiliations: Department of Plastic Surgery, First Hospital of China Medical University, Liaoning 110001, P.R. China
Published online on: November 27, 2012 https://doi.org/10.3892/ol.2012.1047
Pages: 645-650

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Abstract

It has been demonstrated that cyclooxygenase‑2 (COX‑2) is expressed in melanoma tissues and prostaglandin E2 (PGE2) is produced by melanoma cells in vitro. However, the roles of COX‑2/PGE2 in melanoma are largely unknown. In the present study, we set out to analyze the correlation of endogenous PGE2 with the expression of macrophage chemoattractant protein-1 (MCP‑1) and to identify the signaling pathway involved. It was found that MCP‑1 mRNA was heterogeneously expressed in 18 melanoma tissue specimens, and the levels of MCP‑1 mRNA were positively correlated with those of COX‑2 mRNA. Inhibition of endogenous PGE2 production by a COX‑2 inhibitor, COX‑2 siRNA or an NFκB inhibitor suppressed MCP‑1 expression, whereas treatment with TNF‑α (to stimulate endogenous PGE2 production) or exogenous PGE2 enhanced MCP‑1 expression in melanoma cells. Both the EP4 antagonist and the p38 MAPK inhibitor reduced MCP‑1 production in melanoma cells, and abrogated the increased MCP‑1 secretion induced by TNF‑α or exogenous PGE2. Conditioned medium from melanoma cells promoted macrophage migration, which was blocked by inhibitors of the PGE2/EP4/p38 MAPK signaling pathway. These results indicate that endogenous PGE2 induces MCP‑1 expression via EP4/p38 MAPK signaling in an autocrinal manner in melanoma, and melanoma cell‑derived PGE2 may be involved in macrophage recruitment in the melanoma microenvironment.

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