Eicosanoids and other lipid mediators and the tumor hypoxic microenvironment

Hypoxia is a pathological hallmark feature of solid tumors. Though hypoxia is an adverse physiological state, tumors have evolved to utilize this unsuitable environment to their own advantage by activating key biochemical and cellular pathways that are important in progression, survival, and metastasis. Several studies have emphasized the importance of lipid mediators in regulating key biomolecules in the hypoxic microenvironment, for example hypoxia inducible factor-1 (HIF-1), the master regulator of hypoxia. Lipid mediators have been reported to enhance the levels and activity of HIF-1, which subsequently signal to stimulate angiogenesis and tumor cell survival under hypoxic conditions. There are also reports of hypoxia and HIF-1 enhancing the levels of some lipid mediators mostly by upregulating the levels of the enzymes responsible for their biosynthesis. This review gives a brief overview of these two mechanisms and the role played by bioactive lipid mediators in the regulation of tumor progression and survival under hypoxia.