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

Hui Li, Zhenwen Zhao, Gang Wei, Libo Yan, Dongmei Wang, Hong Zhang, George Earl Sandusky, John Turk, Yan Xu

Research output: Contribution to journalArticle

36 Scopus citations

Abstract

Host-tumor cell interactions are recognized to be critical in tumor development. We have shown that group VIA phospholipase A2 [calcium-independent phospholipase A2β (iPLA2β)] is important in regulating extracellular lysophosphatidic acid (LPA) levels around human epithelial ovarian cancer (EOC) cells. To explore the role of iPLA2β in host-tumor cell interactions, we have used immunocompetent iPLA2β knockout (iPLA2β -/-) mice and the mouse EOC cell line ID8. Tumorigenesis and ascites formation were reduced in iPLA2β-/- mice compared with wild-type (WT) mice by more >50% and were reduced further when ID8 cell iPLA2β levels were lowered (by >95%) with shRNA. LPA and lysophosphatidylcholine (LPC) levels in the tumor microenvironment were reduced to ∼80% of WT levels in iPLA2β-/- mice. LPA, but not LPC, stimulated ID8 cell migration and invasion with cells in which iPLA2β expression had been down-regulated in vitro. LPA, but not LPC, also enhanced in vivo ascites formation (by ∼5-fold) and tumorigenesis in iPLA2β-/- mice. This is the first demonstration of a role for host cell iPLA2β in cancer, and these findings suggest that iPLA2β is a potential target for developing novel antineoplastic therapeutic strategies.

Original languageEnglish (US)
Pages (from-to)4103-4116
Number of pages14
JournalFASEB Journal
Volume24
Issue number10
DOIs
StatePublished - Oct 2010

Keywords

  • Lysophosphatidic acid
  • Tumor microenvironment

ASJC Scopus subject areas

  • Biochemistry
  • Biotechnology
  • Genetics
  • Molecular Biology
  • Medicine(all)

Fingerprint Dive into the research topics of 'Group VIA phospholipase A<sub>2</sub> in both host and tumor cells is involved in ovarian cancer development'. Together they form a unique fingerprint.

  • Cite this