Hematogenous Metastasis: Roles of CD44v and Alternative Sialofucosylated Selectin Ligands
- Cite this paper as:
- Konstantopoulos K., Thomas S.N. (2011) Hematogenous Metastasis: Roles of CD44v and Alternative Sialofucosylated Selectin Ligands. In: Wu A. (eds) The Molecular Immunology of Complex Carbohydrates-3. Advances in Experimental Medicine and Biology, vol 705. Springer, Boston, MA
P-selectin, expressed on activated endothelial cells and platelets, is a transmembrane glycoprotein (GP) that mediates, among others, host cell–tumor cell adhesion relevant to the process of hematogenous metastasis. The most compelling evidence for a direct role of P-selectin in the metastatic process is the pronounced inhibition of metastasis in P-selectin-deficient mice compared to wild-type controls in a colon carcinoma cell model [1–3]. Along these lines, enzymatic removal of P-selectin ligands from the colon carcinoma cell surface results in a pronounced reduction of experimental metastasis . Although molecules that bind P-selectin have previously been identified in tumor cell lines [4–6], their functional roles and biological significance have not been substantiated. As has been appropriately argued in the literature , distinctions must be made between molecules that can bind to P-selectin under static conditions in vitro, and functional ligands that do interact with P-selectin under fluid dynamic conditions in vivo. By identifying the functional P-selectin ligand(s) on colon carcinoma cells, using an integrated approach consisting of bioengineering tools and contemporary biochemistry and molecular biology techniques, we provide guidelines for engineering novel therapeutic agents that selectively block tumor cell ligand binding function and thus interfere with metastatic spread. Such a strategy may offer specific antimetastatic efficacy without impairing other important P-selectin-mediated physiological processes [8, 9]. Alternatively, these molecules could be utilized in a targeted drug-delivery approach, which would aim at selectively or preferentially eradicating colon carcinoma cells from the vasculature.