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Tumor cell group via phospholipase A 2 is involved in prostate cancer development
Author(s) -
Li Hui,
Zhang Hong,
Wei Gang,
Cai Qingchun,
Yan Libo,
Xu Yan
Publication year - 2010
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.21251
Subject(s) - tramp , carcinogenesis , prostate cancer , biology , cancer research , metastasis , cell growth , cell , in vivo , cancer , microbiology and biotechnology , cell culture , biochemistry , genetics
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 2 β (iPLA 2 β) in cancers has recently emerged. However, the biological functions of iPLA 2 β in PCa development have been minimally investigated and only in vitro studies have been reported. METHODS We tested the role of iPLA 2 β in host cells using an iPLA 2 β deficient mouse model and the role of iPLA 2 β in tumor cells by comparing the proliferation, migration, and invasion in vitro and tumorigenesis in vivo. CONCLUSIONS iPLA 2 β 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 2 β is not required for PCa tumorigenesis and metastasis. In contrast, when iPLA 2 β 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, iPLA 2 β 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 iPLA 2 β–LPA axis may represent a novel target for PCa. Prostate 77:373–384, 2011. © 2010 Wiley‐Liss, Inc.