Group VIA phospholipase A 2 in both host and tumor cells is involved in ovarian cancer development

ABSTRACT 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.—Li, H., Zhao, Z., Wei, G., Yan, L., Wang, D., Zhang, H., Sandusky, G. E., Turk, J., Xu, Y. Group VIA phospholipase A 2 in both host and tumor cells is involved in ovarian cancer development. FASEB J. 24, 4103–4116 (2010). www.fasebj.org