Expression of N-acetyllactosamine and β1,4-Galactosyltransferase (β4GalT-I) During Adenoma-Carcinoma Sequence in the Human Colorectum

Abstract

We set out to determine the expression profiles of glycoproteins possessing N-acetyllactosamine, a precursor carbohydrate of sialyl Le^x, during colorectal cancer development. We immunohistochemically analyzed the distribution of N-acetyllactosamine as well as of β4GalT-I, a member of the β1,4-galactosyltransferase family responsible for N-acetyllactosamine biosynthesis, in normal mucosa and in adenoma and carcinoma of the human colorectum. Using monoclonal antibody H11, N-acetyllactosamine was barely detectable in the normal mucosa. In low-grade adenoma, however, N-acetyllactosamine was weakly but definitely expressed on the cell surface, and its expression level was moderately increased in high-grade adenoma and markedly increased in carcinoma in situ as well as in advanced carcinoma. To detect β4GalT-I, we used a newly developed polyclonal antibody (designated A18G), which is specific for the stem region of human β4GalT-I. Faint expression of β4GalT-I was detectable in normal mucosa, and the expression level was moderately increased in low-grade adenoma and in high-grade adenoma and markedly increased in carcinoma in situ and advanced carcinoma. The expression of N-acetyllactosamine was highly correlated with the expression of β4GalT-I in these tumor cells. These results indicate that the expression level of β4GalT-I is apparently enhanced during tumorigenesis in the colorectum and that β4GalT-I mostly directs the carcinoma-associated expression of N-acetyllactosamine on the colorectal tumor cell surface.