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 Sandusky, John Turk, Yan Xu

Research output: Contribution to journalArticle

35 Citations (Scopus)

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

Fingerprint

Phospholipases A2
Ovarian Neoplasms
Tumors
Cells
Neoplasms
Lysophosphatidylcholines
Ascites
Cell Communication
Calcium-Independent Phospholipase A2
Carcinogenesis
Tumor Microenvironment
Antineoplastic Agents
Small Interfering RNA
Cell Movement
Demonstrations
Cell Line
lysophosphatidic acid

Keywords

  • Lysophosphatidic acid
  • Tumor microenvironment

ASJC Scopus subject areas

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

Cite this

Group VIA phospholipase A2 in both host and tumor cells is involved in ovarian cancer development. / Li, Hui; Zhao, Zhenwen; Wei, Gang; Yan, Libo; Wang, Dongmei; Zhang, Hong; Sandusky, George; Turk, John; Xu, Yan.

In: FASEB Journal, Vol. 24, No. 10, 2010, p. 4103-4116.

Research output: Contribution to journalArticle

Li, Hui ; Zhao, Zhenwen ; Wei, Gang ; Yan, Libo ; Wang, Dongmei ; Zhang, Hong ; Sandusky, George ; Turk, John ; Xu, Yan. / Group VIA phospholipase A2 in both host and tumor cells is involved in ovarian cancer development. In: FASEB Journal. 2010 ; Vol. 24, No. 10. pp. 4103-4116.
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