Tumor cell group via phospholipase A₂ is involved in prostate cancer development.
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 A₂β (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 iPLA₂β 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 iPLA₂β 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.
Li
Hui
H
Department of Obstetrics and Gynecology, Indiana University, Indianapolis, Indiana 46202, USA.
Zhang
Hong
H
Wei
Gang
G
Cai
Qingchun
Q
Yan
Libo
L
Xu
Yan
Y
D000818:Animals; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation; D054513:Group IV Phospholipases A2 / Q000037:antagonists & inhibitors / Q000502:physiology*; D006801:Humans; D008244:Lysophosphatidylcholines / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009361:Neoplasm Invasiveness; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D011471:Prostatic Neoplasms / Q000201:enzymology / Q000209:etiology*
D008244:Lysophosphatidylcholines; D019869:Phosphatidylinositol 3-Kinases; D054513:Group IV Phospholipases A2