Document Detail


CD44 on LS174T colon carcinoma cells possesses E-selectin ligand activity.
MedLine Citation:
PMID:  15994957     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Metastasis of circulating tumor cells requires a multistep cascade of events initiated by adhesion of tumor cells to the vascular endothelium of involved tissues. This process occurs under the forces of blood flow and is promoted by adhesion molecules specialized to interact under shear conditions. The endothelial molecule E-selectin is a major mediator of these adhesive events, and there is strong evidence that E-selectin receptor-ligand interactions contribute to the formation of metastasis. However, little is known about the identity of E-selectin ligand(s) expressed on cancer cells. To address this issue, we did SDS-PAGE analysis of membrane proteins, metabolic inhibition studies, and blot rolling assays of LS174T, a colon carcinoma cell line known to interact with E-selectin under physiologic flow conditions. Our studies show that LS174T cells express the hematopoietic cell E/L-selectin (HCELL) glycoform of CD44, which functions as a high-affinity E-selectin glycoprotein ligand on these cells. However, in contrast to the HCELL glycoform on human hematopoietic progenitor cells, which expresses carbohydrate-binding determinant(s) for E-selectin primarily on N-glycans of standard CD44, the relevant determinant(s) on LS174T cells is expressed on O-glycans and is predominantly found on variant isoforms of CD44 (CD44v). Our finding that tumor-associated CD44 splice variant(s) express E-selectin ligand activity provides novel perspectives on the biology of CD44 in cancer metastasis.
Authors:
William D Hanley; Monica M Burdick; Konstantinos Konstantopoulos; Robert Sackstein
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Cancer research     Volume:  65     ISSN:  0008-5472     ISO Abbreviation:  Cancer Res.     Publication Date:  2005 Jul 
Date Detail:
Created Date:  2005-07-04     Completed Date:  2005-09-07     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  2984705R     Medline TA:  Cancer Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  5812-7     Citation Subset:  IM    
Affiliation:
Department of Chemical and Biomolecular Engineering, The Johns Hopkins University, Baltimore, Maryland 21218, USA.
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MeSH Terms
Descriptor/Qualifier:
Adenocarcinoma / immunology,  metabolism*,  pathology
Antigens, CD44 / metabolism*
Cell Adhesion / physiology
Cell Line, Tumor
Colonic Neoplasms / immunology,  metabolism*,  pathology
E-Selectin / metabolism*
Electrophoresis, Polyacrylamide Gel
Humans
Ligands
Neoplasm Metastasis
Protein Isoforms
Grant Support
ID/Acronym/Agency:
R01 CA 101135/CA/NCI NIH HHS; R01 HL073714/HL/NHLBI NIH HHS; R01 HL60528/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Antigens, CD44; 0/E-Selectin; 0/Ligands; 0/Protein Isoforms

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