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

Abstract

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/105 cells/24 h) when compared with primary cervical cancers (mean 1.4 mg/mL, range between 0.7 and 2.2 mg/mL/105 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/105 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.

Tissue micro array analysis of ganglioside N-glycolyl GM3 expression and signal transducer and activator of transcription (STAT)-3 activation in relation to dendritic cell infiltration and microvessel density in non-small cell lung cancer

“…N -glycolyl GM3, a monosialic ganglioside, is not expressed in normal human tissues [6], but increased levels of N -glycolyl GM3 were detected in human breast tumors [7]. Gangliosides are also shed in the tumor microenvironment and eventually circulate in patients' blood [8,9]. These circulating gangliosides are thought to be involved in tumor-host interactions facilitating metastasis through tumor immune escape and tumor-associated angiogenesis.…”

Challenges and future perspectives of T cell immunotherapy in cancer

“…Tumour-associated gangliosides, organized in glycosynapses, function as adhesion receptors with consequent activation of signal transducers leading to enhanced tumour cell motility and invasiveness [70–73]. Ganglioside structures may cause deletion or suppression of immune cells and promote tumour angiogenesis and metastasis.…”

Tumor-Associated Glycans and Their Role in Gynecological Cancers: Accelerating Translational Research by Novel High-Throughput Approaches

“…Overexpression of monosialoganglioside GM3 and disialoganglioside GD3 (Figure 1) may correlate with higher malignancy of breast cancer cells by enhancing cell proliferation and migration [165]. Total levels of gangliosides were also observed to be increased in serum and ascites of patients with advanced ovarian cancer [169], indicating the process of shedding or release of gangliosides, which is associated with cancer progression. It was suggested, that shedding of gangliosides into the local tumor microenvironment contributes to tumor strategies to evade immune recognition, thus high concentration of circulating gangliosides is associated with poor prognosis.…”