Document Detail


Knockdown of fucosyltransferase III disrupts the adhesion of circulating cancer cells to E-selectin without affecting hematopoietic cell adhesion.
MedLine Citation:
PMID:  20833389     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Adhesive interactions between selectins and their ligands play an essential role during cancer extravasation. Fucosylation of these proteins by fucosyltransferases, or FUTs, is critical for their functions. Using quantitative RT-PCR, we demonstrated that FUT4 and FUT7 are the predominant FUTs expressed in hematopoietic cell line, while FUT3 is heavily expressed by multiple cancer cell lines including the prostate cancer cell line MDA PCa2b. Knockdown of FUT3 expression in MDA PCa2b cells by small interference RNA (siRNA) significantly reduced FUT3 expression. Cell-surface sialyl Lewis antigens were largely abolished. Cell adhesion and cell rolling on the blood vessel wall were simulated by perfusing cancer cells through microtubes coated with recombinant human E-selectin. At physiological levels of wall shear stress, the number of flowing cancer cells recruited to the microtube surface was dramatically reduced by FUT3 knockdown. Higher rolling velocity was also observed, which is consistent with reduced E-selectin binding activity. Interestingly, FUT3 siRNA treatment also significantly reduced the cell growth rate. Combined with the novel siRNA delivery platform recently developed in our laboratory, FUT3 siRNA could be a promising conjunctive therapy aiming at reducing the metastatic virulence of circulating epithelial cancer cells.
Authors:
Xiaoyan Yin; Kuldeepsinh Rana; Varun Ponmudi; Michael R King
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2010-07-21
Journal Detail:
Title:  Carbohydrate research     Volume:  345     ISSN:  1873-426X     ISO Abbreviation:  Carbohydr. Res.     Publication Date:  2010 Nov 
Date Detail:
Created Date:  2010-10-18     Completed Date:  2011-02-24     Revised Date:  2014-03-24    
Medline Journal Info:
Nlm Unique ID:  0043535     Medline TA:  Carbohydr Res     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  2334-42     Citation Subset:  IM    
Copyright Information:
Copyright © 2010 Elsevier Ltd. All rights reserved.
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MeSH Terms
Descriptor/Qualifier:
Cell Adhesion / drug effects
Cell Proliferation / drug effects
E-Selectin / metabolism*
Fucosyltransferases / biosynthesis,  deficiency*,  genetics
Gene Knockdown Techniques*
Hematopoietic Stem Cells / cytology*
Humans
Ligands
Neoplasms / enzymology*,  pathology*
RNA, Small Interfering / genetics*
Reverse Transcriptase Polymerase Chain Reaction
Structure-Activity Relationship
Tumor Cells, Cultured
Grant Support
ID/Acronym/Agency:
U54 CA143876/CA/NCI NIH HHS; U54CA143876/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/E-Selectin; 0/Ligands; 0/RNA, Small Interfering; EC 2.4.1.-/Fucosyltransferases; EC 2.4.1.65/3-galactosyl-N-acetylglucosaminide 4-alpha-L-fucosyltransferase
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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