Decreased peritoneal ovarian cancer growth in mice lacking expression of lipid phosphate phosphohydrolase 1

PloS One
John NakayamaJill K Slack-Davis

Abstract

Lysophosphatidic acid (LPA) is a bioactive lipid that enhances ovarian cancer cell proliferation, migration and invasion in vitro and stimulates peritoneal metastasis in vivo. LPA is generated through the action of autotaxin or phospholipases, and degradation begins with lipid phosphate phosphohydrolase (LPP)-dependent removal of the phosphate. While the effects of LPA on ovarian cancer progression are clear, the effects of LPA metabolism within the tumor microenvironment on peritoneal metastasis have not been reported. We examined the contribution of lipid phosphatase activity to ovarian cancer peritoneal metastasis using mice deficient in LPP1 expression. Homozygous deletion of LPP1 (LPP1 KO) results in elevated levels and decreased turnover of LPA in vivo. Within 2 weeks of intraperitoneal injection of syngeneic mouse ovarian cancer cells, we observed enhanced tumor seeding in the LPP1 KO mice compared to wild type. However, tumor growth plateaued in the LPP1 KO mice by 3 weeks while tumors continued to grow in wild type mice. The decreased tumor burden was accompanied by increased apoptosis and no change in proliferation or angiogenesis. Tumor growth was restored and apoptosis reversed with exogenous administration of LPA. ...Continue Reading

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Citations

Mar 31, 2015·Journal of Lipid Research·Xiaoyun TangDavid N Brindley
Sep 6, 2020·Biomolecules·Xiaoyun Tang, David N Brindley
Mar 10, 2017·Frontiers in Oncology·Thomas WorzfeldRolf Müller
Aug 23, 2020·International Journal of Molecular Sciences·David N BrindleyMatthew G K Benesch
Feb 12, 2020·Cancers·Matthew G K BeneschDavid N Brindley
Jun 15, 2019·Cell Calcium·Sana KoubaMarie Potier-Cartereau

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