(568s) Glycosphingolipids Are Major E-Selectin Ligands Expressed by Head and Neck Cancer Cells

One of the least understood aspects of cancer is the process of metastasis, or the spread of cancer from the original tumor site to a new organ. In metastasis, cancer cells break off from the primary tumor, travel through the blood stream, attach to the endothelium, and eventually pass through the blood vessel wall to create a new colony in a distant tissue site. However, the molecular mediators of these steps are largely unknown. It is believed that the latter two steps occur through a model parallel to that of leukocyte migration to sites of inflammation, a phenomenon critically dependent on E-selectin located on blood vessel endothelial cells. We hypothesized that head and neck squamous carcinoma cells (HNSCCs) express ligands that can bind to E-selectin, thereby mediating metastasis. Flow cytometry showed that HNSCCs express sialofucosylated molecules that could act as E-selectin ligands, and flow chamber adhesion assays confirmed that HNSCCs bind to cytokine-stimulated endothelial cells in a wholly E-selectin-dependent manner. Enzyme treatment further revealed that sialofucosylated glycolipids are major adhesive ligand(s) for E-selectin, with minimal contribution from glycoproteins. Adsorption of cancer glcyosphingolipids on polystyrene beads further confirmed the E-selectin ligand characteristics of these molecules. With better knowledge of the physics of the binding interaction and biology of the ligand itself, the findings may be used to develop therapeutics or diagnostics to help treat or detect head and neck cancer.