[Modification of glycoconjugates during the carcinogenesis: the case of mammary carcinomas]

Tumour growth is associated with modifications to the structure of glycan residues belonging to the glycoproteins and glycolipids present at the cell surface. These aberrant glycosylations, arising from dysfunction of glycosyltransferases and (or) glycosidases, most often result in a shortening of the glycan chains or an over-expression of structures on the cells that are normally absent or discrete. Some of these changes, such as the expression of antigen Tn in cancers of the breast or colon, appear very early in the evolution of the disease, and can indeed be found in pathologies that are generally considered benign. Most of the cell proteins are glycosylated, including the molecules involved in inter-cell recognition, attachment, cell cycle regulation and apoptosis. The consequences of these disturbances therefore affect many aspects of the biology of the cell and its fate in the body. The impact is particularly evident when the glycan moiety contributes to the functional site of the molecule, the activity of which is then modified or abolished. In addition, the expression of functional residues recognised by molecules with lectin activity, normally restricted to phagocyte cells, is liable to promote metastasis formation by favouring the crossing of the vascular endothelium by tumour cells The identification, using plant lectins and monoclonal antibodies, of oligosaccharides associated with tumour formation, is relevant for both diagnosis, as some glycotopes are expressed before any other cellular anomaly, and prognosis, since certain sequences, e.g., that recognised by L-PHA, reflect dysfunction in the glycan synthesis, culminating in the formation of terminal oside structures that favour the metastatic spread of tumour cells. Therapeutic applications can also be envisaged through action on the tumour glycan antigens by means of naturally-occurring or synthetic immunising entities, or through the use of analogues of sugars that block the activities of the glycosyltransferases or glycosidases responsible for the synthesis of potentially dangerous glycotopes. Beside their practical use, the expression of tumour glycan antigens raises the question of their role in directing the cell towards cancer formation.