C2-O-sLeX glycoproteins are E-selectin ligands that regulate invasion of human colon and hepatic carcinoma cells.

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 promo...

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Autores principales:	Catherine A St Hill, Dahabo Baharo-Hassan, Mariya Farooqui
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2011
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/aea19ace895d4f149e145944ee270f99
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spelling	oai:doaj.org-article:aea19ace895d4f149e145944ee270f992021-11-18T07:00:14ZC2-O-sLeX glycoproteins are E-selectin ligands that regulate invasion of human colon and hepatic carcinoma cells.1932-620310.1371/journal.pone.0016281https://doaj.org/article/aea19ace895d4f149e145944ee270f992011-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21283832/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Similar 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.Catherine A St HillDahabo Baharo-HassanMariya FarooquiPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 1, p e16281 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Catherine A St Hill Dahabo Baharo-Hassan Mariya Farooqui C2-O-sLeX glycoproteins are E-selectin ligands that regulate invasion of human colon and hepatic carcinoma cells.
description	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.
format	article
author	Catherine A St Hill Dahabo Baharo-Hassan Mariya Farooqui
author_facet	Catherine A St Hill Dahabo Baharo-Hassan Mariya Farooqui
author_sort	Catherine A St Hill
title	C2-O-sLeX glycoproteins are E-selectin ligands that regulate invasion of human colon and hepatic carcinoma cells.
title_short	C2-O-sLeX glycoproteins are E-selectin ligands that regulate invasion of human colon and hepatic carcinoma cells.
title_full	C2-O-sLeX glycoproteins are E-selectin ligands that regulate invasion of human colon and hepatic carcinoma cells.
title_fullStr	C2-O-sLeX glycoproteins are E-selectin ligands that regulate invasion of human colon and hepatic carcinoma cells.
title_full_unstemmed	C2-O-sLeX glycoproteins are E-selectin ligands that regulate invasion of human colon and hepatic carcinoma cells.
title_sort	c2-o-slex glycoproteins are e-selectin ligands that regulate invasion of human colon and hepatic carcinoma cells.
publisher	Public Library of Science (PLoS)
publishDate	2011
url	https://doaj.org/article/aea19ace895d4f149e145944ee270f99
work_keys_str_mv	AT catherineasthill c2oslexglycoproteinsareeselectinligandsthatregulateinvasionofhumancolonandhepaticcarcinomacells AT dahabobaharohassan c2oslexglycoproteinsareeselectinligandsthatregulateinvasionofhumancolonandhepaticcarcinomacells AT mariyafarooqui c2oslexglycoproteinsareeselectinligandsthatregulateinvasionofhumancolonandhepaticcarcinomacells
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C2-O-sLeX glycoproteins are E-selectin ligands that regulate invasion of human colon and hepatic carcinoma cells.

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