Histo-blood group A/B antigen deletion/reduction vs. continuous expression in human tumor cells as correlated with their malignancy

Abstract

Deletion or reduction of histo-blood group A or B antigen in tumors of A or B individuals is clearly correlated with the degree of malignancy and metastatic potential in many types of human cancer. Haptotactic motility of A+H- or B+H-colonic or gastric tumor cell lines produced by transfection of A or B gene was significantly lower than that of parental A-H+ or B-H+ cells. This is ascribable to reduced function of α3 or α6/β1 integrin receptor as we have recently shown. However, phenotypic changes resulting from gene transfection may not reflect physiological states associated with deletion or reduction vs. continuous expression of A or B antigen in tumors. We now describe the separation and phenotype characterization of A- cells from A+ tumor cell lines derived originally from colonic tumors of patients with histo-blood group A.A+ and A- populations were detected in originally A+ tumor cell lines SW480 and HT29. A- separated from A+ populations isolated from SW480 and HT29 were characterized by greatly enhanced haptotactic motility associated with reduced or deleted A expression at α3, α6, and β1 integrin receptors which control cell motility. Nevertheless, expression of integrin receptors at the surface of A- populations is the same as that for A+ populations for both SW480 and HT29 cells. Thus, A vs. H glycosylation in integrin receptors may alter their haptotactic function. Cell proliferation as reflected by 3H-thymidine incorporation was also reduced significantly in A+ as compared to A- populations. Our findings indicate that the degree of haptotactic motility and proliferation of colonic tumor cells are physiologically associated with the deletion or reduction vs. continuous expression of the histo-blood group A antigen.