| First Author | Li H | Year | 2010 |
| Journal | FASEB J | Volume | 24 |
| Issue | 10 | Pages | 4103-16 |
| PubMed ID | 20530749 | Mgi Jnum | J:165310 |
| Mgi Id | MGI:4836816 | Doi | 10.1096/fj.10-161356 |
| Citation | Li H, et al. (2010) Group VIA phospholipase A2 in both host and tumor cells is involved in ovarian cancer development. FASEB J 24(10):4103-16 |
| abstractText | 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)beta (iPLA(2)beta)] is important in regulating extracellular lysophosphatidic acid (LPA) levels around human epithelial ovarian cancer (EOC) cells. To explore the role of iPLA(2)beta in host-tumor cell interactions, we have used immunocompetent iPLA(2)beta knockout (iPLA(2)beta(-/-)) mice and the mouse EOC cell line ID8. Tumorigenesis and ascites formation were reduced in iPLA(2)beta(-/-) mice compared with wild-type (WT) mice by more >50% and were reduced further when ID8 cell iPLA(2)beta levels were lowered (by>95%) with shRNA. LPA and lysophosphatidylcholine (LPC) levels in the tumor microenvironment were reduced to approximately 80% of WT levels in iPLA(2)beta(-/-) mice. LPA, but not LPC, stimulated ID8 cell migration and invasion with cells in which iPLA(2)beta expression had been down-regulated in vitro. LPA, but not LPC, also enhanced in vivo ascites formation (by approximately 5-fold) and tumorigenesis in iPLA(2)beta(-/-) mice. This is the first demonstration of a role for host cell iPLA(2)beta in cancer, and these findings suggest that iPLA(2)beta is a potential target for developing novel antineoplastic therapeutic strategies. |
