Tumor cell group via phospholipase A2 is involved in prostate cancer development

Hui Li, Hong Zhang, Gang Wei, Qingchun Cai, Libo Yan, Yan Xu

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

Background Prostate cancer (PCa) is one of the most common malignancies among men in the United States. Further understanding of the molecular mechanisms underlying PCa tumorigenic development is critical for advancing treatment strategies for PCa. The role of Group VIA phospholipase A 2β (iPLA2β) in cancers has recently emerged. However, the biological functions of iPLA2β in PCa development have been minimally investigated and only in vitro studies have been reported. Methods We tested the role of iPLA2β in host cells using an iPLA2β deficient mouse model and the role of iPLA 2β in tumor cells by comparing the proliferation, migration, and invasion in vitro and tumorigenesis in vivo. Conclusions iPLA2β deficiency did not affect tumor development in C57BL/6 mice injected with syngeneic PCa cell line TRAMP-C1P3 in any of three models (subcutaneous, orthotopic, or intratibia injection) tested, suggesting that host cell iPLA 2β is not required for PCa tumorigenesis and metastasis. In contrast, when iPLA2β was down-regulated in TRAMP-C1P3 cells, cell proliferation was reduced in vitro and tumor growth was suppressed in vivo compared to control cells. In particular, iPLA2β was required for lysophosphatidic acid (LPA)-induced migration and invasion in TRAMP-C1P3 cells. We compared human and mouse PCa cells and showed that they shared high similarities in LPA-stimulated effects and signaling pathways. LPA stimulated cell migration and/or invasion via a PI3K-dependent pathway. Together, our results suggest that the tumor cell iPLA2β-LPA axis may represent a novel target for PCa.

Original languageEnglish (US)
Pages (from-to)373-384
Number of pages12
JournalProstate
Volume71
Issue number4
DOIs
StatePublished - Mar 1 2011

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Keywords

  • calcium-independent phospholipase Abeta
  • group VIA phospholipase A (iPLAβ)
  • lysophosphatidic acid (LPA)
  • lysophosphatidylcholine (LPC)
  • prostate cancer (PCa)

ASJC Scopus subject areas

  • Urology
  • Oncology

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