Histo-blood group A/B antigen deletion/reduction vs. continuous expression in human tumor cells as correlated with their malignancy.
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 alpha3 or alpha6/beta1 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 alpha3, alpha6, and beta1 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.
Ichikawa
D
D
Pacific Northwest Research Foundation, Department of Pathobiology, University of Washington, Seattle 98122, USA.
Handa
K
K
Hakomori
S
S
D000017:ABO Blood-Group System / Q000378:metabolism*; D015153:Blotting, Western; D002455:Cell Division / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D003110:Colonic Neoplasms / Q000097:blood* / Q000473:pathology*; D005434:Flow Cytometry; D006801:Humans; D016023:Integrins / Q000378:metabolism; D008099:Liver / Q000502:physiology; D014407:Tumor Cells, Cultured
D000017:ABO Blood-Group System; D016023:Integrins