Journal
CANCER AND METASTASIS REVIEWS
Volume 37, Issue 2-3, Pages 317-334Publisher
SPRINGER
DOI: 10.1007/s10555-018-9731-3
Keywords
Tumor-promoting macrophages; PGE(2); mPGES-1; ALOX5; ALOX-15; cancer
Categories
Funding
- Deutsche Forschungsgemeinschaft [CRC 1039, GRK 2336, FOR 2438]
- Deutsche Krebshilfe [111576, 70112451]
- Else Kroner-Fresenius-Graduiertenkolleg [P2]
- German Cancer Consortium (DKTK)
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The tumor immune landscape gained considerable interest based on the knowledge that genetic aberrations in cancer cells alone are insufficient for tumor development. Macrophages are basically supporting all hallmarks of cancer and owing to their tremendous plasticity they may exert a whole spectrum of anti-tumor and pro-tumor activities. As part of the innate immune response, macrophages are armed to attack tumor cells, alone or in concert with distinct T cell subsets. However, in the tumor microenvironment, they sense nutrient and oxygen gradients, receive multiple signals, and respond to this incoming information with a phenotype shift. Often, their functional output repertoire is shifted to become tumor-supportive. Incoming and outgoing signals are chemically heterogeneous but also comprise lipid mediators. Here, we review the current understanding whereby arachidonate metabolites derived from the cyclooxygenase and lipoxygenase pathways shape the macrophage phenotype in a tumor setting. We discuss these findings in the context of cyclooxygenase-2 (COX-2) and microsomal prostaglandin E synthase-1 (mPGES-1) expression and concomitant prostaglandin E-2 (PGE(2)) formation. We elaborate the multiple actions of this lipid in affecting macrophage biology, which are sensors for and generators of this lipid. Moreover, we summarize properties of 5-lipoxygenases (ALOX5) and 15-lipoxygenases (ALOX15, ALOX15B) in macrophages and clarify how these enzymes add to the role of macrophages in a dynamically changing tumor environment. This review will illustrate the potential routes how COX-2/mPGES-1 and ALOX5/-15 in macrophages contribute to the development and progression of a tumor.
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