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Screening of enzymatic synthesis and expression of Lewis determinants in human colorectal carcinoma.
Fernández-Briera, Almudena; Cuevas, Elisa; Gil-Martín, Emilio.
Afiliação
  • Fernández-Briera A; Universidad de Vigo.
  • Cuevas E; Complejo Hospitalario Universitario de Ourense.
  • Gil-Martín E; BIOQUÍMICA, GENÉTICA & INMUNOLOGÍA, FACULTAD DE BIOLOGÍA, ESPAÑA.
Rev Esp Enferm Dig ; 107(10): 598-607, 2015 Oct.
Article em En | MEDLINE | ID: mdl-26437978
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- Le(a)/Le(x)- and difucosylated -Le(b)/Le(y)- 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 alpha(1,2/3/4)FT activities involved in the sequential fucosylation of cores 1 and 2 showed significant increases in tumour tissue. Expressed as microU/mg and control vs. tumour activity (pfrom Wilcoxon's test), the FT activities for Le(a)/Le(b) synthesis were: lacto-N-biose alpha(1,2)/alpha(1,4)FT, 65.4 ± 19.0 vs. 186 ± 35.1 (p< 0.005); lacto-N-fucopentaose 1 alpha(1,4)FT, 64.9 ± 11.9 vs. 125.4 ± 20.7 (p< 0.005); Le(a) alpha(1,2)FT, 56.2 ± 7.2 vs. 130.5 ± 15.6 (p< 0.001). Similarly, for Le(x)/Le(y) synthesis were: N-acetyllactosamine alpha(1,2)-/alpha(1,3)FT, 53.4 ± 12.2 vs. 108.1 ± 18.9 (p< 0.001); 2'-Fucosyl-N-acetyllactosamine alpha(1,3)FT, 61.3 ± 10.7 vs. 126.4 ± 22.9 (p< 0.001); 2'-Fucosyllactose alpha(1,3)FT, 38.9 ± 10.9 vs. 143.6 ± 28.9 (p< 0.001); 2'-Methyllactose alpha(1,3)FT, 30.9 ± 4.8 vs. 66.1 ± 8.1 (p< 0.005); and Le(x) alpha(1,2)FT, 54.3 ± 11.9 vs. 88.2 ± 14.4 (p< 0.001). Immunohistochemical Le(y) 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 Le(y), probably at the expense of Le(x).
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias Colorretais / Antígenos do Grupo Sanguíneo de Lewis Tipo de estudo: Diagnostic_studies / Screening_studies Limite: Aged / Female / Humans / Male / Middle aged Idioma: En Revista: Rev Esp Enferm Dig Assunto da revista: GASTROENTEROLOGIA Ano de publicação: 2015 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias Colorretais / Antígenos do Grupo Sanguíneo de Lewis Tipo de estudo: Diagnostic_studies / Screening_studies Limite: Aged / Female / Humans / Male / Middle aged Idioma: En Revista: Rev Esp Enferm Dig Assunto da revista: GASTROENTEROLOGIA Ano de publicação: 2015 Tipo de documento: Article