Increased levels of gangliosides in the plasma and ascitic fluid of patients with advanced ovarian cancer.

摘要

OBJECTIVES: To assess the expression of total gangliosides in primary ovarian cancer cell lines, ascitic fluid and plasma of advanced ovarian cancer patients. DESIGN: A prospective study. SETTING: The Department of Obstetrics and Gynecology at the University of Arkansas for Medical Sciences and the Laboratory of Glycolipid Immunotherapy, John Wayne Cancer Institute. POPULATION: Twenty-two women diagnosed with advanced ovarian cancer and seven normal female controls. METHODS: Total gangliosides shedding from primary ovarian cancer cell lines were measured by estimating lipid-associated sialic acids (LASAs test) and compared with the ganglioside levels shed by primary cervical and uterine cancer cell lines. In addition, plasma and ascitic samples from advanced ovarian cancer patients were collected at the time of surgery and analysed for the presence of total gangliosides. MAIN OUTCOME MEASURES: Levels of total ganglioside in plasma and ascites fluid samples drawn from ovarian cancer patients, relative to total gangliosides levels in plasma from normal female controls. RESULTS: All primary ovarian tumours secreted high levels of total gangliosides (mean 4 mg/mL, range between 2.7 and 4.8 mg/mL/10(5) cells/24 h) when compared with primary cervical cancers (mean 1.4 mg/mL, range between 0.7 and 2.2 mg/mL/10(5) cells/24 h) (P < 0.008) and uterine carcinoma cell lines (mean 1.4 mg/mL, range between 1.3 and 1.6 mg/mL/10(5) cells/24 h) (P <.004). Elevated levels of total gangliosides were detected in the plasma [mean (SD) 31 (12) mg/mL, range between 18 and 57 mg/mL] (P <.001), and in the peritoneal fluid [mean (SD) 27 (9) mg/mL, range between 14 and 40 mg/mL] (P <.003) of ovarian cancer patients when compared with the levels detectable in the plasma samples of normal female controls tested [mean (SD) 15 (2) mg/mL, range between 12 and 18 mg/mL]. CONCLUSIONS: Increased serum levels of total gangliosides may reflect shedding or release of gangliosides from the surface of ovarian tumour cells. Secretion of gangliosides may play an important role in the inhibition of anti-tumour immune function commonly observed in advanced ovarian cancer.