Functional role of glycosphingolipids in tumor progression.

Molecular modeling of glycosphingolipids (GSLs), and their organization in membranes, suggest that GSL "patches" provide binding sites for interaction with ligands and adjacent cells, and that GSLs or their catabolites modulate transmembrane signaling. Aberrant GSL expression is a ubiquitous phenotype common to essentially all types of tumors, and leads to (i) formation of tumor-associated antigens defined by a large variety of monoclonal anti-bodies; (ii) aberrant adhesion favoring metastasis and invasiveness of tumor cells; and (iii) aberrant catabolism leading to altered transmembrane signaling and loss of growth control. Classical immunotherapy is based on (i). New approaches termed "antiadhesion" and "anti-signaling" therapy, based on (ii) and (iii), are hereby proposed.