Cyclooxygenases, prostanoids, and tumor progression

Abstract

In response to various growth factors, hormones or cytokines, arachidonic acid can be mobilized from phospholipids pools and converted to bioactive eicosanoids through cyclooxygenase (COX), lipoxygenase (LOX) or P-450 epoxygenase pathway. The COX pathway generates five major prostanoids (prostaglandin D₂, prostaglandin E₂, prostaglandin F_2α, prostaglandin I₂ and thromboxane A₂) that play important roles in diverse biological processes. Studies suggest that different prostanoids and their own synthase can play distinct roles in tumor progression and cancer metastasis. COX-2 and PGE₂ synthase have been most well documented in the regulation of various aspects of tumor progression and metastasis. PGE₂, for example, can stimulate angiogenesis or other signaling pathways by binding to its receptors termed EPs. Therefore, targeting downstream prostanoids may provide a new avenue to impede tumor progression. In this review, aberrant expression and functions of several prostanoid synthetic enzymes in cancer will be discussed. The possible regulation of tumor progression by prostaglandins and their receptors will also be discussed.