Publisher Summary Aberrant glycosylation is the most common phenomenon associated with oncogenic transformation expressed in cell membranes of animal and human cancer cells. Such aberrant structures at the surface membranes may well be effective targets in prevention, diagnosis, and treatment of human cancer. Many of the aberrant glycosylation products can be recognized by specific MAbs as tumor-associated carbohydrate antigens. Many of these antigens have been identified as carbohydrates, thus there is increasing evidence that essentially all human cancers are characterized by aberrant glycosylation. Aberrant glycosylation as such may be the basis of inappropriate cell/cell and cell/matrix interactions that may be reflected in the abnormal cell social behavior of tumor cells, such as uncontrolled cell growth, invasiveness, and metastatic potential. Whatever the genetic or epigenetic basis of expression of aberrant glycosylation is, the phenomenon is of crucial importance in understanding the antisocial behavior of tumor cells as well as in practical applications in diagnosis and treatment of human cancer.

Aberrant glycosylation in tumors and tumor-associated carbohydrate antigens

A current trend in cell biology is to study the mechanisms of regulatory cellular function through specific structural and func tional molecules, i.e., growth factors, their receptors, membrane transporters, cytoskeletal systems, surface membrane and pericellular components, etc., rather than classical enzymes. The key molecules involved in such functional regulation are modified by 2 major chemical processes, phosphorylation and glycosylation. A greal deal of interest has been focused on phosphorylation as a ubiquitous and essential modulatory mechanism of cellular function. This idea has been greatly reinforced by the fact that many transforming genes (cellular as well as viral oncogenes) encode phosphoproteins, which by themselves are protein kinases, although the functions of many of their substrates have not been identified (see, for a review, Ref. 9). Less attention has been paid to the functional significance of glycosylation than to that of phosphorylation; nevertheless, the changes in glycosylation occur as quickly and dramatically as the process of phosphorylation at various stages of develop ment, differentiation, and oncogenesis (see, for a review, Ref. 38). While phosphorylation patterns are few, the patterns of glycosylation are numerous; over 100 types of glycosylated structures have been characterized among those bound to lipids (ceramides), i.e., glycolipids (see, for a review, Ref. 39). Similar variation of glycosylation can also be found in the peripheral region of carbohydrates in glycoproteins, in addition to the structural variation in the core region of carbohydrate chains bound to proteins through Nor O-glycosides (see, for reviews, Refs. 42 and 65). In contrast to phosphorylation, which directly modulates pro tein function, glycosylation affects the conformation, localization, and organization of functional and structural proteins; thus, glycosylation determines the turnover and organizational frame work of proteins within cytoplasm, membranes, and the pericellular matrix (see, for reviews, Refs. 42 and 87). LJpidglycosylation in membranes, particularly cell surface membranes, offers cell recognition sites for cell-social events and may regulate the function of membrane proteins such as receptors and adhesive proteins (38, 115) (Table 1). With the functional significance of

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Aberrant glycosylation in cancer cell membranes as focused on glycolipids: overview and perspectives.

Cette revue met l'accent sur quelques sujets d'evolution recente: 1) chimie des marqueurs glycolipidiques associes aux tumeurs et regis par le developpement; 2) facteurs affectant l'expression des glycolipides a la surface des cellules, et 3) application possible des marqueurs glycolipidiques au traitement et au diagnostic du cancer humain

Glycosphingolipids as tumor-associated and differentiation markers.

Mouse monoclonal antibody AbR24 has a high degree of specificity for human melanoma cells when tested on viable cultured cells using the protein A mixed hemagglutinin serological assay. The antigen detected by this antibody has been isolated from melanoma cells and shown to be GD3 ganglioside by compositional and partial structural analysis and by comparison with authentic GD3 in thin layer chromatography (TLC). AbR24 reacts with authentic GD3, but not with any other ganglioside tested. Using TLC and reactivity with AbR24, a wide range of cells and tissues was examined for the presence of GD3. A new serological assay, termed glycolipid-mediated immune adherence, was devised for assaying the reactivity of AbR24 with gangliosides. Melanomas (cultured cells or tumor tissue) were shown to have GD3 and GM3 as major gangliosides. Other cells and tissues examined also contained GD3, but usually only in low amounts. Melanomas (and MOLT-4, a T cell line) were characterized by a simplified ganglioside profile with GD3 and GM3 as major components. The apparent discrepancy between the ubiquitous presence of GD3 and the serological specificity of AbR24 for melanoma cells can be explained in terms of localization and concentration of GD3 in different cells.

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GD3, a prominent ganglioside of human melanoma. Detection and characterisation by mouse monoclonal antibody.

Simultaneous quantitative analysis of bioactive sphingolipids by high-performance liquid chromatography-tandem mass spectrometry

Correlation between changes in blood fatty acid composition and visual sustained attention performance in children with inattention: effect of dietary n−3 fatty acids containing phospholipids

The lipid pattern of thirteen human melanoma tumors from various tissues were investigated. In seven of the tumors, an estimate was given about the proportion of malignant melanocytes to the total cell population, and a reverse correlation was determined between the proportion of malignant cells in these tumors and their neutral lipid content. The phospholipids did not show any modification, nor did the cholesterol in the cancerous tissues. The ganglioside pattern was found to be similar in all analyzed samples, with GM3, GM2 and GD3 as major components, although no correlation was found between the malignant level and the ganglioside content of the tumors.

https://febs.onlinelibrary.wiley.com/doi/pdf/10.1111/j.1432-1033.1979.tb12866.x

Lipid Composition of Human Malignant Melanoma Tumors at Various Levels of Malignant Growth

Alteration of gangliosides in plasma and red cells of humans bearing melanoma tumors.

Improved two-dimensional solvent system for thin-layer chromatographic analysis of polar lipids on silica gel 60 precoated plates

We studied: (1) concentrations and fatty acid compositions of plasma non-esterified fatty acids, neutral lipids, and phospholipids, and (2) fatty acid composition of flight muscle phospholipids in wintering, premigratory, and spring and fall migrating western sandpipers (Calidris mauri). Plasma neutral lipid and phospholipid levels were elevated in migrants, reflecting high rates of fat deposition. An important role of phospholipids in fattening is suggested by the fact that the amount of fatty acids in plasma phospholipids was similar to, or in spring as much as twice, that of neutral lipids. Changes in the ratio of plasma neutral lipids to phospholipids may indicate seasonal changes in triacylglycerol stores of invertebrate prey. Monounsaturation and total unsaturation of plasma neutral lipids and phospholipids increased during migration. Muscle phospholipids were more monounsaturated in spring and fall, but total unsaturation was reduced in fall. Arachidonic acid [20:4(n-6)] was especially abundant in muscle phospholipids in winter (29%) and declined during migration (19–22%), contributing to a decline in the ratio of n-6 to n-3 fatty acids. The abundance of plasma phospholipids and variability of neutral lipid to phospholipid ratio indicates that measurement of plasma phospholipids will improve methods for assessment of fattening rates of birds. The functional significance of changes in muscle phospholipids is unclear, but may relate to depletion of essential n-6 fatty acids during exercise.

Georges Zwingelstein

Papers

Correlation between changes in blood fatty acid composition and visual sustained attention performance in children with inattention: effect of dietary n−3 fatty acids containing phospholipids

Lipid Composition of Human Malignant Melanoma Tumors at Various Levels of Malignant Growth

Alteration of gangliosides in plasma and red cells of humans bearing melanoma tumors.

Improved two-dimensional solvent system for thin-layer chromatographic analysis of polar lipids on silica gel 60 precoated plates

Plasma and muscle phospholipids are involved in the metabolic response to long-distance migration in a shorebird.