Screening of enzymatic synthesis and expression of Lewis determinants in human colorectal carcinoma
Rev. esp. enferm. dig
; 107(10): 598-607, oct. 2015. tab, ilus
Article
in English
| IBECS
| ID: ibc-141423
Responsible library:
ES1.1
Localization: BNCS
ABSTRACT
BACKGROUND:
Although colorectal carcinogenesis has been intensively studied, the published investigations do not provide a consistent description of how different carbohydrate determinants of colorectal epithelium are modified in colorectal cancer (CRC).OBJECTIVE:
This study is an attempt to characterize the terminal fucosylation steps responsible for the synthesis of mono- (Lea/Lex) and difucosylated (Leb/Ley) Lewis antigens in healthy and tumour CRC tissue.METHODS:
An immunohistochemical study of Lewis antigens' expression was undertaken, along with screening of the fucosyltransferase (FT) activities involved in their synthesis, on healthy and tumour samples from 18 patients undergoing CRC.RESULTS:
Analysis of a(1,2/3/4)FT activities involved in the sequential fucosylation of cores 1 and 2 showed significant increases in tumour tissue. Expressed as mU/mg and control vs. tumour activity (p from Wilcoxon's test), the FT activities for Lea/ Leb synthesis were lacto-N-biose a(1,2)/a(1,4)FT, 65.4 ± 19.0 vs. 186 ± 35.1 (p < 0.005); lacto-N-fucopentaose 1 a(1,4)FT, 64.9 ± 11.9 vs. 125.4 ± 20.7 (p < 0.005); Lea a(1,2)FT, 56.2 ± 7.2 vs. 130.5 ± 15.6 (p < 0.001). Similarly, for Lex/Ley synthesis were N-acetyllactosamine a(1,2)-/a(1,3)FT, 53.4 ± 12.2 vs. 108.1 ± 18.9 (p < 0.001); 2'-Fucosyl-N-acetyllactosamine a(1,3)FT, 61.3 ± 10.7 vs. 126.4 ± 22.9 (p < 0.001); 2'-Fucosyllactose a(1,3)FT, 38.9 ± 10.9 vs. 143.6 ± 28.9 (p < 0.001); 2'-Methyllactose a(1,3) FT, 30.9 ± 4.8 vs. 66.1 ± 8.1 (p < 0.005); and Lex a(1,2)FT, 54.3 ± 11.9 vs. 88.2 ± 14.4 (p < 0.001). Immunohistochemical Ley expression was increased (p < 0.01 according to Wilcoxon's test) in tumour tissue, with 84.6% of specimens being positive 7.7% weak, 15.4% moderate and 61.5% high intensity.CONCLUSIONS:
Results suggest the activation of the biosynthesis pathways of mono- and difucosylated Lewis histo-blood antigens in tumour tissue from CRC patients, leading to the overexpression of Ley, probably at the expense of Lex
Full text:
Available
Collection:
National databases
/
Spain
Database:
IBECS
Main subject:
Oligosaccharides
/
Immunohistochemistry
/
Colorectal Neoplasms
/
Lewis X Antigen
/
Fucosyltransferases
Type of study:
Diagnostic study
/
Screening study
Limits:
Female
/
Humans
/
Male
Language:
English
Journal:
Rev. esp. enferm. dig
Year:
2015
Document type:
Article
Institution/Affiliation country:
Complejo Hospitalario Universitario/Spain
/
University of Vigo/Spain