[Frontiers in Bioscience 16, 3233-3251, June 1, 2011]

Interactions between endothelial selectins and cancer cells regulate metastasis

Catherine A. St. Hill1

1Department of Veterinary Clinical Sciences, University of Minnesota, Room C339, Veterinary Medical Center, 1352 Boyd Avenue, St. Paul, MN 55108, USA

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. Characteristics of selectins and their ligands 3.1. Structure and localization of selectins
3.2. Expression and function of selectin ligands
3.3. Interactions of selectins with endothelial cells
3.4. Functions of E-selectin and P-selectin in disease
3.5. Factors that regulate E-selectin and P-selectin expression
3.6. Selectins and selectin ligands mediate signal transduction
4. Roles of selectin: selectin ligand interactions in cancer metastasis
4.1. Selectins regulate tumor cell extravasation
4.2. The involvement of selectin ligands in cancer metastasis
5. The role of selectins and their ligands in cancer inflammation
6. Clinical applications of selectin-ligand interactions in cancer
7. Conclusions and future perspectives
8. Acknowledgements
9. References

1. ABSTRACT

The selectins: E-selectin, P-selectin, and L-selectin are adhesion molecules that are crucial for binding of circulating leukocytes to vascular endothelium during the inflammatory response to injury or infection. Accumulated evidence indicates that selectins regulate adhesion of circulating cancer cells to the walls of blood vessels. Selectin ligands are transmembrane glycoproteins expressed on leukocytes and cancer cells that promote bond formations with selectins to mediate inflammatory processes. Selectins and selectin ligands also participate in signal transduction to regulate diverse cellular functions. Sialyl Lewis X (sLex) and sialyl Lewis A (sLea) tetrasaccharides are carbohydrate motifs displayed on protein or lipid scaffolds that are critical components of functional selectin ligands. Selectin binding to sLex and sLea present on colon, gastric, bladder, pancreatic, breast, and prostate carcinomas enhances distant organ metastasis. High expression of sialyl Lewis ligands on these cancers is significantly correlated with a poor post-operative prognosis. This review will focus on the roles of E-selectin and P-selectin in cancer progression. Understanding the role of selectins in cancer supports the development of novel selectin-based therapies to control metastasis.