Tumor cell-derived prostaglandin E2 inhibits monocyte function by interfering with CCR5 and Mac-1

Reinhard Zeidler*, Miklos Csanady, Olivier Gires, Stephan Lang, Bärbel Schmitt, Barbara Wollenberg

*Corresponding author for this work
46 Citations (Scopus)


The cyclooxygenases (COX)-1 and COX-2 are key enzymes in the conversion of arachidonic acid to prostaglandins and other eicosanoids. Whereas COX-1 is expressed ubiquitously, COX-2 is an immediate-early gene often associated with malignant transformation, and a role for the COX enzymes in tumor initiation and promotion is discussed. Nonsteroidal anti-inflammatory drugs (NSAIDs) like aspirin and indomethacin that block COX-1 and -2 have been shown to have beneficial effects for tumor patients. Therefore, these compounds have gained interest also among oncologists. However, the molecular mechanism by which NSAIDs inhibit carcinogenesis is not clearly understood. The prostaglandin-dependent and -independent effect may both account for their antineoplastic action. We show here that minor cells derived from different tumors regularly produce prostaglandin E2 (PGE2) interfering with the function of monocytes. In particular, PGE2 inhibits the potential of monocytes to migrate in the direction of a chemotactic stimulus and to adhere to endothelial cell. This inhibition is most probably due to a modulation of the chemokine receptor CCR5 and the β2-integrin Mac-1. Both down-regulation of CCR5 and reduced expression of Mac-1 may diminish the potential of peripheral blood monocytes to leave blood vessels and invade target tissues. Since both dysfunctions can be restored with NSAIDs, our findings help to explain the molecular chemopreventive action of NSAIDs on tumor formation and progression.

Original languageEnglish
JournalFASEB Journal
Issue number5
Pages (from-to)661-668
Number of pages8
Publication statusPublished - 2000


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