Expression of type a and b tumor necrosis factor (TNF) receptors on melanoma cells can be regulated by dbc-AMP and IFN-γ

✍ Scribed by Stefan Carrel; Françoise Hartmann; Suzanne Salvi; Hugo Albrecht; Magali Schreyer; Donata Rimoldi

• Publisher: John Wiley and Sons
• Year: 1995
• Tongue: French
• Weight: 966 KB
• Volume: 62
• Category: Article
• ISSN: 0020-7136
• DOI: 10.1002/ijc.2910620115

✦ Synopsis

Local administration of high-dose r-TNFa with IFNy in the limbs of melanoma patients has proved to be a very promising treatment. To understand the role played by the effect of TNF on melanoma cells in tumor destruction, we have investigated the expression of TNF-receptors in melanoma cells using monoclonal antibodies specific for the type-A (75-kDa) and the type-B (55-kDa) TNF receptors. Flow cytometric analysis of cultured melanoma cells indicated the presence of both types of receptor. Quantificative differences in the relative levels of receptors were observed for different cells lines, although the type-B receptor was generally more strongly expressed. Similar results were obtained by immunohistochemistry on cryosections from tumor samples. Positive staining of variable intensity was observed for the type-B TNF-receptor in a high percentage of tumor cells. The type-A TNF-receptor was also detected, but with a weaker staining. The total TNF-binding activity of cultured melanoma cells, as measured by binding of t*SI-labeled TNFa, was up-regulated between 2and 4-fold by incubation of cells with activators of protein kinase A or IFNy. Treatment of cultured melanoma cells with dbc-AMP resulted in a selective induction of type-A TNF-receptors, without affecting the type-B receptor level. In contrast, IFNy was able to induce either type of receptor in a cell-line-dependent fashion. Addition of TNFa to melanoma cells induced the activation of the nuclear transcription factor .B, as measured in an electrophoretic mobility shift assay, thus indicating the biological significance of the TNF-receptors on these cells.