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Pathophysiological effects of human TNF‐alpha‐producing tumor xenografts in immunosuppressed mice
Author(s) -
Nagy T.,
J´nossy T.,
Vizler C.,
Bohus K.,
Jóa F.,
Végh P.,
Duda E.
Publication year - 1999
Publication title -
apmis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.909
H-Index - 88
eISSN - 1600-0463
pISSN - 0903-4641
DOI - 10.1111/j.1699-0463.1999.tb01490.x
Subject(s) - tumor necrosis factor alpha , cytotoxic t cell , genetic enhancement , hela , necrosis , biology , transplantation , transfection , immunology , medicine , cancer research , cell , cell culture , endocrinology , pathology , gene , in vitro , biochemistry , genetics
Groups of CBA mice immunosuppressed with antithymocyte serum (ATS) treatment were xeno‐transplanted with either HeLa human cervical carcinoma cells or genetically modified cells expressing the human tumor necrosis factor‐α (TNF) gene (All cells). Both cell lines were highly resistant to the cytotoxic effects of TNF. If 3 times 10 6 tumor cells were inoculated s.c. into female mice, HeLa cells grew progressively into large tumors and killed 74% of the recipients, while TNF‐expressing All cells caused fatal tumor growth only in 22% of the mice. 3times 10 6 or 1.5times 10 7 All cells produced progressive tumor growth and lethality in all male recipients. In sera of all the All‐cell‐transplanted mice, biologically active TNF was detected shortly (4.5 h) after tumor inoculation (6–39 U/ml), decreasing to below detection level in the circulation by day 3. In recipients of 15 million All cells, circulating TNF reappeared and reached high levels (12–1000 U/ml) 3 to 7 weeks later, when the animals bore large tumors (14–23 mm). Generally, such mice became cachectic, severely anemic, hypothermic, and soon died. On account of calcium mobilization from bones, their serum Ca levels were high. Electron microscopy revealed severe liver damage, but there were no signs of chronic arthritis. These results suggest that ATS‐treated mice xenotransplanted with TNF‐gene‐transfected All human tumor cells provide a new model for studying the pathophysiological and anti‐tumor effects of TNF.