α(1,2)fucosylation in human colorectal carcinoma

Abstract

Lewis(b) and Lewis(y) (Le) antigens are known to be elevated in colorectal tumours. Alterations in the catalytic behaviour of GDP-L-fucose:β-D-galactoside α(1,2)fucosyltransferase [α(1,2)FT, EC: 2.4.1.69], the key enzyme in their synthesis, have been suggested as being responsible for these changes. In particular, an aberrant tumour-specific α(1,2)FT activity that converts Le(a) and Le(x) to Le(b) and Le(y) determinants, respectively, has been reported in colorectal cancer tissues. To clarify the catalytic function of this enzyme during colorectal tumorigenesis, we analyzed α(1,2)FT activity levels in healthy and tumour colon specimens using different acceptor substrates and determined the kinetic properties of the enzyme. To complete the study, the aberrant Le(a)/Le(x) α(1,2)fucosylation was determined in healthy and tumour colorectal tissues. A correlation analysis between the activity levels and various standard clinicopathological features, such as tumour stage, was also carried out to elucidate the role of these activities in tumour progression. The results obtained confirm the enhanced α(1,2)fucosylation in colorectal neoplastic tissues and the importance of the aberrant Le(a)/Le(x) α(1,2)FT activity in this increase. However, taking into account the high levels of Le(a)/Le(x) fucosylation observed in healthy control tissues, we must rule out the idea of a colorectal tumour-specific α(1,2)FT. On the other hand, no significant association was observed between α(1,2)FT activity levels and the clinicopathological characteristics. Overall, our results suggest that α(1,2)FT activity plays a critical role in the accumulation of Le(b) and Le(y) antigens in human colorectal carcinoma.