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.
Department of Obstetrics and Gynecology, Indiana University, 975 W. Walnut St. IB355A, Indianapolis, IN 46202, USA.
Hui
H
Li
Zhenwen
Z
Zhao
Gang
G
Wei
Libo
L
Yan
Dongmei
D
Wang
Hong
H
Zhang
George Earl
GE
Sandusky
John
J
Turk
Yan
Y
Xu
D000818:Animals; D001483:Base Sequence; D015153:Blotting, Western; D002460:Cell Line; D005260:Female; D054509:Group X Phospholipases A2 / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D010051:Ovarian Neoplasms / Q000201:enzymology / Q000473:pathology*; D012313:RNA / Q000737:chemistry; D020133:Reverse Transcriptase Polymerase Chain Reaction
D012313:RNA; D054509:Group X Phospholipases A2