PMID- 21283832
OWN - NLM
STAT- MEDLINE
DCOM- 20110802
LR  - 20211020
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 6
IP  - 1
DP  - 2011 Jan 19
TI  - C2-O-sLeX glycoproteins are E-selectin ligands that regulate invasion of human 
      colon and hepatic carcinoma cells.
PG  - e16281
LID - 10.1371/journal.pone.0016281 [doi]
LID - e16281
AB  - Similar to mechanisms of recruitment of activated leukocytes to inflamed tissues, 
      selectins mediate adhesion and extravasation of circulating cancer cells. Our 
      objective was to determine whether sialyl Lewis X modified core 2 O-glycans 
      (C2-O-sLe(X)) present on colon and hepatic carcinoma cells promote their adhesion 
      and invasion. We examined membrane expression of C2-O-sLe(X), selectin binding, 
      invasion of human colon and hepatic carcinoma cell lines, and mRNA levels of 
      alpha-2,3 fucosyltransferase (FucT-III) and core 2 beta-1,6 
      N-acetylglucosaminyltransferase (C2GnT1) genes, necessary for C2-O-sLe(X) 
      synthesis, by quantitative reverse-transcriptase (RT) PCR. Synthesis of core 2 
      branched O-glycans decorated by sLe(X) is dependent on C2GnT1 function and thus 
      we determined enzyme activity of C2GnT1. The cell lines that expressed C2GnT1 and 
      FucT-III mRNA by quantitative RT-PCR were highly positive for C2-O-sLe(X) by flow 
      cytometry, and colon carcinoma cells possessed highly active C2GnT1 enzyme. Cells 
      bound avidly to E-selection but not to P- and L-selectin. Gene knock-down of 
      C2GnT1 in colon and hepatic carcinoma cells using short hairpin RNAs (shRNA) 
      resulted in a 40-90% decrease in C2-O-sLe(X) and a 30-50% decrease in E-selectin 
      binding compared to control cells. Invasion of hepatic and colon carcinoma cells 
      containing C2GnT1 shRNA was significantly reduced compared to control cells in 
      Matrigel assays and C2GnT1 activity was down-regulated in the latter cells. The 
      sLe(X) epitope was predominantly distributed on core 2 O-glycans on colon and 
      hepatic carcinoma cells. Our findings indicate that C2GnT1 gene expression and 
      the resulting C2-O-sLe(X) carbohydrates produced mediate the adhesive and 
      invasive behaviors of human carcinomas which may influence their metastatic 
      potential.
FAU - St Hill, Catherine A
AU  - St Hill CA
AD  - Department of Veterinary Clinical Sciences, University of Minnesota, St. Paul, 
      Minnesota, United States of America. sthil001@umn.edu
FAU - Baharo-Hassan, Dahabo
AU  - Baharo-Hassan D
FAU - Farooqui, Mariya
AU  - Farooqui M
LA  - eng
GR  - K08 CA111829/CA/NCI NIH HHS/United States
GR  - 5KO8CA111829-04/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20110119
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (CY 1503)
RN  - 0 (E-Selectin)
RN  - 0 (Epitopes)
RN  - 0 (Glycoproteins)
RN  - 0 (Ligands)
RN  - 0 (Oligosaccharides)
RN  - 0 (RNA, Messenger)
RN  - EC 2.4.1.- (N-Acetylglucosaminyltransferases)
RN  - EC 2.4.1.102 (beta-1,3-galactosyl-O-glycosyl-glycoprotein 
      beta-1,6-acetylglucosaminyl transferase)
SB  - IM
MH  - Carcinoma, Hepatocellular/chemistry/*pathology
MH  - Cell Adhesion
MH  - Cell Line, Tumor
MH  - Colonic Neoplasms/chemistry/*pathology
MH  - E-Selectin/*metabolism
MH  - Epitopes/analysis
MH  - Glycoproteins/analysis/physiology
MH  - Humans
MH  - Ligands
MH  - N-Acetylglucosaminyltransferases/genetics
MH  - Neoplasm Invasiveness/*pathology
MH  - Oligosaccharides/analysis/*physiology
MH  - RNA, Messenger/analysis
PMC - PMC3023807
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2011/02/02 06:00
MHDA- 2011/08/04 06:00
PMCR- 2011/01/19
CRDT- 2011/02/02 06:00
PHST- 2010/10/04 00:00 [received]
PHST- 2010/12/09 00:00 [accepted]
PHST- 2011/02/02 06:00 [entrez]
PHST- 2011/02/02 06:00 [pubmed]
PHST- 2011/08/04 06:00 [medline]
PHST- 2011/01/19 00:00 [pmc-release]
AID - PONE-D-10-02821 [pii]
AID - 10.1371/journal.pone.0016281 [doi]
PST - epublish
SO  - PLoS One. 2011 Jan 19;6(1):e16281. doi: 10.1371/journal.pone.0016281.