Role of prostaglandins in tumor microenvironment

Tumor tissue is composed of tumor cells and surrounding non-tumor endothelial and immune cells, collectively known as the tumor microenvironment. Tumor cells manipulate tumor microenvironment to obtain sufficient oxygen and nutrient supply, and evade anti-tumor immunosurveillance. Various types of signaling molecules, including cytokines, chemokines, growth factors, and lipid mediators, are secreted, which co-operate to make up the complex tumor microenvironment. Prostaglandins, cyclooxygenase metabolites of arachidonic acid, are abundantly produced in tumor tissues. Ever since treatment with nonsteroidal anti-inflammatory drugs showed anti-tumor effect in mouse models and human patients by inhibiting whole prostaglandin production, investigators have focused on the importance of prostaglandins in tumor malignancies. However, most studies that followed focused on the role of an eminent prostaglandin, prostaglandin E₂, in tumor onset, growth, and metastasis. It remained unclear how other prostaglandin species affected tumor malignancies. Recently, we identified prostaglandin D₂, a well-known sleep-inducing prostaglandin, as a factor with strong anti-angiogenic and anti-tumor properties, in genetically modified mice. In this review, we summarize recent studies focusing on the importance of prostaglandins and their metabolites in the tumor microenvironment.