Abstract
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.
| Original language | English (US) |
|---|---|
| Title of host publication | Advances in Experimental Medicine and Biology |
| Pages | 601-619 |
| Number of pages | 19 |
| Volume | 705 |
| DOIs | |
| State | Published - 2011 |
Publication series
| Name | Advances in Experimental Medicine and Biology |
|---|---|
| Volume | 705 |
| ISSN (Print) | 00652598 |
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Keywords
- CD44
- Colon carcinoma cells
- Metastasis
- Selectin
- Shear flow
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)
- Medicine(all)
Cite this
Hematogenous metastasis : Roles of CD44v and alternative sialofucosylated selectin ligands. / Konstantopoulos, K; Thomas, Susan N.
Advances in Experimental Medicine and Biology. Vol. 705 2011. p. 601-619 (Advances in Experimental Medicine and Biology; Vol. 705).Research output: Chapter in Book/Report/Conference proceeding › Conference contribution
}
TY - GEN
T1 - Hematogenous metastasis
T2 - Roles of CD44v and alternative sialofucosylated selectin ligands
AU - Konstantopoulos, K
AU - Thomas, Susan N.
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
UR - http://www.scopus.com/inward/record.url?scp=80054023220&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=80054023220&partnerID=8YFLogxK
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
VL - 705
T3 - Advances in Experimental Medicine and Biology
SP - 601
EP - 619
BT - Advances in Experimental Medicine and Biology
ER -