Bioactive lysolipids in cancer and angiogenesis

While normal angiogenesis is critical for development and tissue growth, pathological angiogenesis is important for the growth and spread of cancers by supplying nutrients and oxygen as well as providing a conduit for distant metastasis. The interaction among extracellular matrix molecules, tumor cells, endothelial cells, fibroblasts, and immune cells is critical in pathological angiogenesis, in which various angiogenic growth factors, chemokines, and lipid mediators produced from these cells as well as hypoxic microenvironment promote angiogenesis by regulating expression and/or activity of various related genes. Sphingosine 1-phosphate and lysophosphatidic acid, bioactive lipid mediators which act via specific G protein-coupled receptors, play critical roles in angiogenesis. In addition, other lipid mediators including prostaglandin E₂, lipoxin, and resolvins are produced in a stimulus-dependent manner and have pro- or anti-angiogenic effects, presumably through their specific GPCRs. Dysregulated lipid mediator signaling pathways are observed in the contxt of some tumors. This review will focus on LPA and S1P, two bioactive lipid mediators in their regulation of angiogenesis and cell migration that are critical for tumor growth and spread.