Eicosanoid Regulation of Angiogenesis in Tumors

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Tumor angiogenesis, the formation of new capillary blood vessels in tumors from pre-existing vasculature, is required for tumor growth and progression. Eicosanoids, the bioactive lipids derived from arachidonic acid, possess potent and diverse biological activities. In response to stimuli, arachidonic acid is mobilized from phospholipid pools and metabolized by cyclooxygenases (COX), lipoxygenases (LOX), and p450 epoxygenases (EOX) to form a variety of eicosanoids. The involvement of eicosanoids in tumor angiogenesis and progression is implicated by the observations that nonsteroidal anti-inflammation drugs (NSAIDs) reduce tumor growth and angiogenesis. Subsequently, it is found that the levels of COX-2 and/or 12-LOX are frequently increased in various cancers. Further studies using molecular and pharmacological approaches have found that COX-2 and 12-LOX, when overexpressed in carcinoma cells, enhance their angiogenic potential and stimulate tumor growth. In this article, we discuss how COX and LOX in cancer cells modulate tumor angiogenesis and present the possibility of using NSAIDs and LOX inhibitors as antiangiogenesis agents.

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