Cytotoxicity induced by recombinant human tumor necrosis factor-alpha dependent on the types of its receptors on canine cells.
Based on the recent findings that show how recombinant human tumor necrosis factor (rh-TNF)-alpha has potent antitumor activity on human cancer patients when it locally administrated, we have tested the cytotoxicity of rh-TNF-alpha on 3 canine cultured cells: (1) canine kidney carcinoma (CKCa-1), (2) mastocytoma and (3) Mardin Darby canine kidney cells (MDCK). The cell surface expression of TNF-alpha receptors on these canine cells was also determined with anti-human TNF RI and RII polyclonal antibodies. Our data shows that on CKCa-1 which has TNF RI receptors rh-TNF-alpha induced cytotoxicity. By contrast, it exhibited no toxicity on canine mastocytoma which has mainly RII receptors. The data also suggest actinomycin D (ACT-D), an anticancer antibiotic, enhanced the cytotoxicity of rh-TNF-alpha. Combined with ACT-D, rh-TNF-alpha showed the cytotoxicity on MDCK which possessed both TNF RI and RII receptors. The results indicate that the cytotoxicity of rh-TNF-alpha depends on the presence of TNF RI receptors on canine tumor cells.
Aoki
M
M
Department of Veterinary Surgery, College of Agriculture, Osaka Prefecture University, Japan.
Sasaki
N
N
Nomura
K
K
Katamoto
H
H
Kubo
K
K
Kodama
H
H
Mukamoto
M
M
Shimada
T
T
Ohashi
F
F
D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects*; D004283:Dog Diseases / Q000473:pathology; D004285:Dogs; D006367:HeLa Cells; D006801:Humans; D007668:Kidney; D007680:Kidney Neoplasms / Q000473:pathology / Q000662:veterinary; D008214:Lymphocytes / Q000166:cytology / Q000187:drug effects; D012515:Mast-Cell Sarcoma / Q000473:pathology / Q000662:veterinary; D011994:Recombinant Proteins / Q000633:toxicity*; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology / Q000633:toxicity*
D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha