Cell-surface bound complement regulatory activity is necessary for the in vivo survival of KDH-8 rat hepatoma.
The monoclonal antibody 5I2 recognizes and functionally inhibits a Crry-like complement regulator molecule on rat cells (corresponding to human decay accelerating factor and membrane cofactor protein activity). The inhibition of complement regulatory activity by 5I2 antibody results in complement deposition on rat cell membranes exposed to homologous complement. Two subclones of KDH-8 rat hepatoma were selected for the experiments; one expressing high (CrryH) and the second low (CrryL) amounts of Crry-like antigen. Both sublines grow in vivo in syngeneic rats, but at lower cell doses (< 10(5) cells/rat) the survival time of rats injected with CrryL cells is prolonged. Injection of tumour-bearing rats with 5I2 monoclonal antibody intraperitoneally did not influence the tumour growth. However, it resulted in 50% mortality within a few hours, accompanied by severe haemorrhage in the peritoneal cavity. Pretreatment of the tumour cells with 5I2 monoclonal antibody or its F(ab')2 fragment substantially increased the survival time of recipient rats. Even permanent survivors were found, indicating that cell membrane-associated complement regulatory activity, which provides protection against attack of homologous complement, is necessary for in vivo tumour growth.
Department of Molecular Biology, Nagoya City University School of Medicine, Japan.
L
L
Baranyi
K
K
Baranji
H
H
Takizawa
N
N
Okada
H
H
Okada
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000954:Antigens, Surface; D003176:Complement C3 / Q000378:metabolism; D015938:Complement Membrane Attack Complex / Q000096:biosynthesis; D005260:Female; D008114:Liver Neoplasms, Experimental / Q000276:immunology* / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009363:Neoplasm Proteins / Q000032:analysis / Q000276:immunology*; D009368:Neoplasm Transplantation; D051381:Rats; D011919:Rats, Inbred Strains; D011956:Receptors, Cell Surface; D011951:Receptors, Complement / Q000032:analysis / Q000502:physiology*; D017463:Receptors, Complement 3b
D000911:Antibodies, Monoclonal; D000954:Antigens, Surface; D003176:Complement C3; D015938:Complement Membrane Attack Complex; C081470:Cr1l protein, mouse; C513105:Cr1l protein, rat; D009363:Neoplasm Proteins; D011956:Receptors, Cell Surface; D011951:Receptors, Complement; D017463:Receptors, Complement 3b