Group VIA phospholipase A2 in both host and tumor cells is involved in ovarian cancer development

Host-tumor cell interactions are recognized to be critical in tumor development. We have shown that group VIA phospholipase A(2) [calcium-independent phospholipase A(2)β (iPLA(2)β)] is important in regulating extracellular lysophosphatidic acid (LPA) levels around human epithelial ovarian cancer (EOC) cells. To explore the role of iPLA(2)β in host-tumor cell interactions, we have used immunocompetent iPLA(2)β knockout (iPLA(2)β(-/-)) mice and the mouse EOC cell line ID8. Tumorigenesis and ascites formation were reduced in iPLA(2)β(-/-) mice compared with wild-type (WT) mice by more >50% and were reduced further when ID8 cell iPLA(2)β levels were lowered (by>95%) with shRNA. LPA and lysophosphatidylcholine (LPC) levels in the tumor microenvironment were reduced to ∼80% of WT levels in iPLA(2)β(-/-) mice. LPA, but not LPC, stimulated ID8 cell migration and invasion with cells in which iPLA(2)β expression had been down-regulated in vitro. LPA, but not LPC, also enhanced in vivo ascites formation (by ∼5-fold) and tumorigenesis in iPLA(2)β(-/-) mice. This is the first demonstration of a role for host cell iPLA(2)β in cancer, and these findings suggest that iPLA(2)β is a potential target for developing novel antineoplastic therapeutic strategies.