Molecular mechanisms of expression of Lewis b antigen and other Type I Lewis antigens in human colorectal cancer

Lewis b (Le(b)) antigens are gradiently expressed from the proximal to the distal colon, i.e., they are abundantly expressed in the proximal colon, but only faintly in the distal colon. In the distal colon, they begin to increase at the adenoma stage of cancer development and then increase with cancer progression. We aimed to clarify the molecular basis of Le(b) antigen expression in correlation with the expression of other type I Le,vis antigens, such as Lewis a (sLe(a)) and sialylated Lewis a (sLe(a)), in colon cancer cells. Considering the Se genotype and the relative activities of the H and Se enzymes, the amounts of Le(b) antigens were proved to be determined by both the H and Se enzymes in noncancerous and cancerous colon tissues. But the Se enzyme made a much greater contribution to determining the Le(b) amounts than the H enzyme. In noncancerous colons, the Se enzyme were gradiently expressed in good correlation with the Le(b) expression, while the H enzyme was constantly expressed throughout the whole colon. In distal colon cancers, the H and Se enzymes were both significantly upregulated in comparison with in adjacent noncancerous tissues. In proximal colon cancers, expression of the H enzyme alone was highly augmented. The augmented expression of Le(b) antigens in distal colon cancers is caused mainly by upregulation of the Se enzyme and partly by the H enzymes, while it is caused by upregulation of the H enzyme alone in proximal colon cancers, The Se gene dosage profoundly influences the amounts of the Le(b), Le(a), and sLe(a) antigens in whole colon tissues, regardless of whether they are noncancerous or cancerous tissues. It suggests that the Se enzyme competes with alpha 2,3 sialyltransferase(s) and the Le enzyme for the type I acceptor substrates.