Tiazofurin induces a down-modulation of ICAM-1 expression on K562 target cells impairing NK adhesion and killing.
Tiazofurin treatment of K562 leukemia cells in vitro depletes the metabolites of the guanylate biosynthetic pathway, inducing erythroid differentiation, that, in turn, alters the phenotypic profile. As a consequence, K562 cells possibly modify their interaction with immune cells. Here we describe the binding and killing activity of peripheral blood NK cells against differentiating K562 cells and the correlation between their altered binding capacity and ICAM-1 expression levels in differentiating K562 cells. We found that decreased percentages of NK (and T) cells were bound to differentiating K562 cells generating a decreased cytotoxic activity. This corresponded to decreased expression of ICAM-1, as detected by FACS analysis and Western blot. Erythroid differentiation, binding and killing reduction, and ICAM-1 down-modulation were completely abrogated by guanosine treatment. Tiazofurin causes a decrease in lymphocyte recognition and binding to K562 target cells. This can be ascribed to the down-modulation of ICAM-1 expression on target cells, which, therefore, can escape killing, acquiring a selective survival advantage.
Zamai
L
L
Istituto di Anatomia Umana Normale, Università di Bologna, Italy.
Zauli
G
G
Bavelloni
A
A
Marmiroli
S
S
Cataldi
A
A
Weber
G
G
Vitale
M
M
D015703:Antigens, CD / Q000096:biosynthesis / Q000187:drug effects; D000970:Antineoplastic Agents / Q000494:pharmacology*; D018968:CD58 Antigens; D002448:Cell Adhesion / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis* / Q000187:drug effects*; D007694:Killer Cells, Natural / Q000166:cytology*; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000187:drug effects; D012254:Ribavirin / Q000031:analogs & derivatives* / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D015703:Antigens, CD; D000970:Antineoplastic Agents; D018968:CD58 Antigens; D008562:Membrane Glycoproteins; D018799:Intercellular Adhesion Molecule-1; D012254:Ribavirin; C033706:tiazofurin