Abstract
Increase of ganglioside content on sera of tumor-bearing patients has been observed in many types of cancer and determinations of serum ganglioside profiles have shown that the altered ganglioside species are always the major ones present in the corresponding tumors. Upon surgical treatment of the tumors, the serum ganglioside content returns to normal values, thus suggesting that increased gangliosides in the blood derive from proliferating cancer cells. Shedding involves all cellular ganglosides, but the rate of shedding depends on the ceramide structure, and it is much higher for molecular species containig C16-C20 fatty acids (i.e. the lower band of ganglioside doublets seen by thin-layer chromatography). The mechanism of ganglioside shedding leading to the alteration of the serum profile is not fully understood, but it is very likely that gangliosides are shed as monomeric molecules. Indeed, when micellar gangliosides are injected i.v. to rats, the serum protein distribution at equilibrium show a higher affinity of high density lipoproteins and significant binding to albumin, whereas tumor-shed gangliosides display the same distribution as endogenous gangliosides with the highest proportion on low density lipoproteins and none on alubmin. In vivo, shed gangliosides that are taken up by erythrocytes and leukocytes have an immuno-modulatory effect. Low concentrations might be immunogenic and higher amounts lead to an inhibition of the immune response, although the extent of inhibition gangliosdides depends on the structure of both oligosaccharide and ceramide moieties. The most potent effect concerns the production of interleukin-1 by macrophages and the activity of released interleukin-1 on thymocytes.
