Inhibition of tumor cell growth in vitro by murine monoclonal antibodies that recognize a proliferation-associated cell surface antigen system in rats and humans.
The mouse monoclonal antibody (MoAb) B3 raised against a rat bladder cancer cell line and the MoAbs HBJ127 and HBJ98 raised against a human bladder cancer cell line recognize homologous antigens predominantly present on proliferating cells of the corresponding species. Examination of MoAb-defined antigen and epitopes revealed that both HBJ127 and HBJ98 MoAbs defined a human cell surface glycoprotein complex having an apparent molecular weight of 125,000-130,000 which was composed of a heavy subunit of a glycoprotein nature (Mr 90,000-95,000) and a disulfide-linked light subunit of protein nature (Mr 30,000-35,000), but the HBJ127 and HBJ98 MoAbs recognized a protein epitope and a sugar epitope on the heavy subunit, respectively. Likewise, the B3 MoAb recognized a protein epitope on the heavy subunit of a rat cellular glycoprotein complex of similar composition to the HBJ127/HBJ98-defined human antigen. Addition of the B3 MoAb to rat and the HBJ127 or HBJ98 MoAb to human tumor cells inhibited the nucleic acid synthesis or the proliferation of the tumor cells in vitro in a dose-dependent manner. The target tumor cells exposed to MoAb could regrow when they were freed from the antibody, indicating that the effect of these MoAbs on the tumor cells is cytostatic and reversible. These MoAbs did not cause down-regulation of the cell surface antigen and did not arrest the cell cycle in a certain phase. These observations indicate that the Mr 125,000 glycoprotein cell surface component detected in both rat and human systems may play a requisite role for cell proliferation and that our MoAbs could inhibit the function by binding to the functionally proximal region of the component.
H
H
Yagita
T
T
Masuko
Y
Y
Hashimoto
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D000918:Antibody Specificity; D000936:Antigen-Antibody Complex; D000954:Antigens, Surface / Q000276:immunology*; D002453:Cell Cycle; D002462:Cell Membrane / Q000502:physiology*; D004247:DNA / Q000096:biosynthesis; D004705:Endocytosis; D000939:Epitopes; D006023:Glycoproteins / Q000502:physiology; D006801:Humans; D006918:Hydroxyurea / Q000494:pharmacology; D008565:Membrane Proteins / Q000502:physiology*; D008970:Molecular Weight; D012313:RNA / Q000096:biosynthesis; D051381:Rats; D001749:Urinary Bladder Neoplasms / Q000473:pathology
D000911:Antibodies, Monoclonal; D000936:Antigen-Antibody Complex; D000954:Antigens, Surface; D000939:Epitopes; D006023:Glycoproteins; D008565:Membrane Proteins; D012313:RNA; D004247:DNA; D006918:Hydroxyurea