Alterations of Lewis histo-blood group antigen expression in cancer cells

摘要

Carcinogenesis in various tissues is accompanied by alterations in protein and lipid glycosylation, such as changes in the expressions of Lewis histo-blood group antigens. Neoplastic transformation is often followed by changes in expression of one or more of these oligosaccharides in a pattern that is typical for the tissue. These alterations correlate with changes in the expressions of specific glycosyltransferases. Overexpression of Lewis antigens in some types of cancer might be a significant prognostic factor. Upregulation of Lewis^y, Lewis^b, and other α1,2-fucosylated oligosaccharides is linked to an increased tendency to metastasis and resistance to treatment. For example, invasive breast cancer of poor prognosis reveals high expression levels of Lewis^y and Lewis^b. Lewis^x is also overexpressed in breast cancer cells. Overexpression of Lewisa also occurs in precancerous states of stomach tissue. Upregulation of sialyl Lewis^a correlates with the metastatic potential of colon and pancreatic malignancies and inversely with survival rate of patients. A similar relation was observed between sialyl Lewis^x overexpression and malignancies of the lungs, prostate, urinary bladder, stomach, breast, kidney, and liver. Some of the Lewis antigens are ligands of specific receptors and adhesion molecules. For example, Lewis^x is recognized by scavenger receptor C-type lectin (SRCL), which belongs to the group of innate immunity receptors. Sialyl Lewis^a and sialyl Lewis^x specifically interact with E- and P-selectins, which are key molecules in leukocyte rolling process. Ongoing research shows an increasing number of potential therapeutic applications related to the upregulation of Lewis antigens.