Cancer and inflammation: an aspirin a day keeps the cancer at bay

Abstract

Live imaging of the interactions between oncogene-transformed cells and leukocytes in zebrafish reveals that PGE(2) promotes the survival and proliferation of cancer cells. Non-steroid anti-inflammatory drugs, like aspirin, are the effective inhibitors of PGE(2) production and could be used with other anti-tumor agents in the treatment of cancer.

Figure 1

PGE₂ produced by leukocytes near cancer cells acts as a pro-survival signal through the EP1 receptor. (A) The pathways involved in eicosanoid metabolism in the cytoplasm of a leukocyte approaching a cancer cell are shown, together with the chemical or genetic (morpholino) inhibitors that block specific enzymes. (B) Different PGE₂ receptors (EP1–4) and their association with specific G-protein subunits lead to the activation of different pathways. Protein kinase A (PKA) activation downstream of EP2 or EP4 signaling stabilizes β-catenin (Wnt) and P-ERK (Ras) signals to increase proliferation. EP1 receptors were also found in a perinuclear compartment, where other, as yet unknown mechanisms may lead to transcriptional and epigenetic changes. See text for details and references.