Targeting Cell Surface Nucleolin in Cancer

Enhanced expression of the multi-functional protein nucleolin (NCL) is observed on the surface of activated lymphocytes, angiogenic endothelial and many different types of cancer cells. Translocation of NCL at the external side of the plasma membrane occurs via a secretory pathway independent of the endoplasmic reticulum- Golgi complex, requires intracellular intact actin cytoskeleton, and seems to be mediated by a variety of factors. Cell surface NCL serves as a binding partner of several molecules implicated in cell differentiation, adhesion and leukocyte trafficking, inflammation, angiogenesis and tumor development, mediating their biological activities and in some cases, leading to their internalization. Accumulating evidence validates cell surface NCL as a strategic target for treatment of cancer, while its property of tumor-specific uptake of targeted ligands seems to be useful for the development of non-invasive imaging tools for the diagnosis of cancer and for the targeted release of chemotherapeutic drugs. This chapter summarizes papers and patents related to the redistribution and the biological functions of cell surface NCL, with emphasis on the potential importance and advantages of developing efficient anticell surface NCL strategies.

Keywords: Angiogenesis , aptamers, cancer, cell surface nucleolin, colorectal cancer, conjugated chemotherapeutic drugs, endostatin, erbB tyrosine kinase receptors, esophageal squamous cell carcinoma, glioblastoma, growth factors, hepatocellular carcinoma, ligand specific internalization, papillary thyroid carcinoma, pleiotrophin, pseudopeptides, receptor protein tyrosine phosphatase beta/zeta, targeted delivery approaches, tumor-homing peptide F3, vascular endothelial growth factor.