Gangliosides as Signaling Regulators in Cancer

At the plasma membrane, gangliosides, a group of glycosphingolipids, are expressed along with glycosphingolipids, phospholipids, and cholesterol in so-called lipid rafts that interact with signaling receptors and related molecules. Most cancers present abnormalities in the intracellular signal transduction system involved in tumor growth, invasion, and metastasis. To date, the roles of gangliosides as regulators of signal transduction have been reported in several cancer types. Gangliosides can be expressed by the exogenous ganglioside addition, with their endogenous expression regulated at the enzymatic level by targeting specific glycosyltransferases. Accordingly, the relationship between changes in the composition of cell surface gangliosides and signal transduction has been investigated by controlling ganglioside expression. In cancer cells, several types of signaling molecules are positively or negatively regulated by ganglioside expression levels, promoting malignant properties. Moreover, antibodies against gangliosides have been shown to possess cytotoxic effects on ganglioside-expressing cancer cells. In the present review, we highlight the involvement of gangliosides in the regulation of cancer cell signaling, and we explore possible therapies targeting ganglioside-expressing cancer.

Prognostic Significance of Tumor Tissue NeuGcGM3 Ganglioside Expression in Patients Receiving Racotumomab Immunotherapy

Expression of N-glycolyl GM3 (NeuGcGM3) ganglioside was detected in the tumor specimens of patients who were on Racotumomab anti-idiotype vaccine maintenance treatment, and prognostic significance as a biomarker was investigated. No statistically significant association was observed in the multivariate analysis between overall survival and tissue NeuGcGM3 IHC levels. Although numerically there was a difference favoring less intense IHC for better prognosis, this did not reach statistical power. However, there was a strong correlation between Racotumomab doses and overall survival (OS). Mean OS of the patient with more than 10 Racotumomab application was significantly longer than the patient who had less than 10 injections (70.7 months vs. 31.1 months, p<0.001). We propose that, regardless of staining intensity, the presence of NeuGcGM3 in patient tissues might be an indicator of benefit in Racotumomab treatment.

Expression of ganglioside GD2 on colorectal adenocarcinoma cells

Using flow cytometry GD2 ganglioside expression was evaluated both on colorectal adenocarcinoma cell lines and on tumor tissue samples from colorectal cancer patients. The marker was found on EpCAM-positive tumor cells in 6 of 12 patients' samples but not on the HT29 and CaCo-2 cell lines. GD2 expression was not an exceptional feature of cancer stem cells, since its expression level was similar on CD133-positive and CD133-negative tumor cells. Thus, the presence of GD2 ganglioside was revealed on colorectal adenocarcinoma cells for the first time. This finding makes it possible to use targeted therapy to treat this disease.

Dietary Control of Ganglioside Expression in Mammalian Tissues

Gangliosides are series of glycosphingolipids containing sialic acids in the oligosaccharide portion in mammalian cells. Gangliosides are a component of cellular membranes and play roles in modulating membrane function and the activity of membrane proteins. Abnormal expression and metabolism of gangliosides lead to the onset of several conditions in humans, such as neurologic diseases, diabetes, and cancer. A number of studies have been carried out to date to investigate the role of gangliosides in these diseases, and the effect of diet on tissue expression of gangliosides has recently become a topic of interest in this field. As gangliosides are degraded in the intestinal tract, ingested food-derived gangliosides are not directly absorbed into tissues in vivo, but the degradation products can be absorbed and affect ganglioside expression in the tissues. Recent studies have also shown that the expression of gangliosides in tissue cells can be indirectly induced by controlling the expression of ganglioside metabolism-related genes via the diet. These results indicate that dietary control can regulate the expression levels of gangliosides in tissues, which is expected to play a role in preventing and treating ganglioside-related diseases. This review introduces recent studies on the effect of diet on the expression of gangliosides in tissues, with a focus on our findings.

Gangliosides: The Double-Edge Sword of Neuro-Ectodermal Derived Tumors

Gangliosides, the glycosphingolipids carrying one or several sialic acid residues, are mostly localized at the plasma membrane in lipid raft domains and implicated in many cellular signaling pathways mostly by interacting with tyrosine kinase receptors. Gangliosides are divided into four series according to the number of sialic acid residues, which can be also modified by O-acetylation. Both ganglioside expression and sialic acid modifications can be modified in pathological conditions such as cancer, which can induce either pro-cancerous or anti-cancerous effects. In this review, we summarize the specific functions of gangliosides in neuro-ectodermal derived tumors, and their roles in reprogramming the lipidomic profile of cell membrane occurring with the induction of epithelial-mesenchymal transition.