Secretory phospholipase 2 (sPLA2) in carcinogenesis and tumor microenvironment

Phospholipases A2 (PLA2s) are ubiquitous enzymes that play crucial roles as lipid mediators, promoting the release of fatty acids and lysophospholipids (LPLs) from glycerophospholipids (GPLs). The most commonly known function of PLA2 is host defense; however, as PLA2 is an important mediator of inflammation, its aberrant regulation may cause disease pathology, including carcinogenesis. Secretory PLA2 (sPLA2) is a calcium-dependent lipolytic enzyme, and its enzymatic functions, in addition to nonenzymatic interactions, play fundamental roles in normal tissue homeostasis. sPLA2 is mainly responsible for the release of arachidonic acid and, therefore, a major initiator of lipid signaling and inflammation. This chapter covers the roles of the sPLA2 enzyme superfamily with an emphasis on group IIA (sPLA2-IIA) in inflammation, tumor progression, and tumor microenvironment regulation by focusing on the underlying molecular mechanisms, as well as current therapeutic approaches.