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

FASEB J. 2010 Oct;24(10):4103-16. doi: 10.1096/fj.10-161356. Epub 2010 Jun 8.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Blotting, Western
  • Cell Line
  • Female
  • Group X Phospholipases A2 / metabolism*
  • Mice
  • Mice, Knockout
  • Neoplasm Invasiveness
  • Neoplasm Metastasis
  • Ovarian Neoplasms / enzymology
  • Ovarian Neoplasms / pathology*
  • RNA / chemistry
  • Reverse Transcriptase Polymerase Chain Reaction

Substances

  • RNA
  • Group X Phospholipases A2