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.
