TY - GEN
T1 - Hematogenous metastasis
T2 - Roles of CD44v and alternative sialofucosylated selectin ligands
AU - Konstantopoulos, Konstantinos
AU - Thomas, Susan N.
N1 - Funding Information:
This work was supported, in whole or in part, by National Institutes of Health Grant R01 CA101135 (NCI).
PY - 2011
Y1 - 2011
N2 - 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 [1]. 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 [7], 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.
AB - 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 [1]. 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 [7], 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.
KW - CD44
KW - Colon carcinoma cells
KW - Metastasis
KW - Selectin
KW - Shear flow
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U2 - 10.1007/978-1-4419-7877-6_32
DO - 10.1007/978-1-4419-7877-6_32
M3 - Conference contribution
C2 - 21618132
AN - SCOPUS:80054023220
SN - 9781441978769
T3 - Advances in Experimental Medicine and Biology
SP - 601
EP - 619
BT - The Molecular Immunology of Complex Carbohydrates-3
A2 - Wu, Albert
ER -