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. Together, these observations demonstrate that the elevated levels of LPA per se in LPP1 KO mice do not inhibit tumor growth. Rather, the data support the notion that either elevated LPA concentration or altered LPA metabolism affects other growth-promoting contributions of the tumor microenvironment.
HighlightsDesmoplastic small round cell tumor of the ovary is a rare clinical entity with poor prognosis.Accurate diagnosis utilizes a combination of histological, immunohistological, and cytogenetic findings.This disease should be kept on the differential diagnosis in young women with widespread disease on presentation.
Wasp sting is a relatively common arthropod assault, but is sometimes fatal because of anaphylaxis. Rhabdomyolysis is a serious condition, with destruction of striated muscles, and can be induced by various causes such as drugs, heart attacks, CRASH syndrome, and viper bites. Mass envenomation by multiple wasp stings can also cause rhabdomyolysis followed by acute renal failure, although it is extremely rare. We herein report a case who had an anaphylaxis-like reaction and rhabdomyolysis due to multiple wasp stings.
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