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Tumor Necrosis Factor as an Autocrine Growth Factor for Neuroblastoma¹

Laboratoire d'Immunologie, Centre Léon Bérard, 28 rue Laënnec, 69373 Lyon Cedex 8, France

Recombinant tumor necrosis factor (TNF) stimulates the proliferation of two neuroblastoma cell lines, SKNFI and SKNBE, in both serum-free medium and fetal calf serum-supplemented medium but has no effect in medium without insulin. This effect is very similar with TNF doses ranging from 5 to 500 ng/ml but depends on the duration of treatment; when cells are treated for 168 h with TNF, the maximal index of proliferation is observed between 120 and 144 h of treatment. The two neuroblastoma cell lines express type A and type B TNF receptors and contain TNF protein; however, TNF is undetectable in culture supernatants. Treatment of the two neuroblastoma cell lines with a rabbit polyclonal antibody to TNF for 96 h fully inhibits [³H]thymidine incorporation; less than 5% viable cells are left in the samples after treatment. A combination of two monoclonal antibodies against type A and type B TNF receptors also inhibits over 85% of the [³H]thymidine incorporation by the two cell lines after 96 h of treatment; the use of a single antibody has a partial effect, suggesting that both receptors are functional on the neuroblastoma cell lines. Taken together, these results show that TNF is an autocrine growth factor for the two neuroblastoma cell lines SKNFI and SKNBE. The results described above have been confirmed on two other neuroblastoma cell lines, IRM32 and CLB-PE.

¹ This work has benefited from the support of the Comité du Rhône and Comité de la Saône et Loire of the French National League against Cancer. E. G. has been awarded a fellowship grant by the Comité de la Haute-Savoie and the Comité de la Saône et Loire of the French National League against Cancer.

² To whom requests for reprings should be addressed.

Received 11/26/91. Accepted 3/20/92.