Tumour necrosis factor-alpha stimulates invasiveness of T-cell hybridomas and cytotoxic T-cell clones by a pertussis toxin-insensitive mechanism.
Tumour necrosis factor-alpha (TNF-alpha) stimulated invasion by mouse T-cell hybridomas and cytotoxic T-lymphocyte clones into rat embryo fibroblast monolayers. The effect on these highly invasive cells was limited: invasion was stimulated maximally to 130% of controls. However, when cells were pretreated with pertussis toxin (PT), which inhibits invasion to +/- 20% of controls, a clearcut effect was observed: 400 U TNF-alpha per ml stimulated invasion usually two- to threefold, and sometimes even up to 10-fold. Therefore, experiments were done with PT-pretreated cells. Stimulation was dose dependent and maximal at 200-400 U TNF-alpha per ml. An anti-TNF-alpha monoclonal antibody completely abolished TNF-alpha-induced invasion. The effect was maximal 30 min after addition of cells and TNF-alpha to the monolayer and then declined. TNF-alpha preincubation of T-cell hybridoma cells, but not of fibroblasts, had a similar stimulatory effect, which was also maximal after 30 min. This shows that TNF-alpha acts directly on the T-cell hybridoma cells. Invasive T-cell hybridomas colonize many tissues from the blood similarly as normal T cells. Our data thus suggest that TNF-alpha can stimulate migration of normal T lymphocytes into inflamed tissues and can promote metastasis of malignant T lymphomas. The signals involved are transmitted via a pertussis toxin-insensitive pathway.
La Rivière
G
G
The Netherlands Cancer Institute, Amsterdam.
Klein Gebbinck
J W
JW
Schipper
C A
CA
Roos
E
E
D000818:Animals; D002465:Cell Movement / Q000276:immunology; D002478:Cells, Cultured; D005347:Fibroblasts / Q000276:immunology; D006825:Hybridomas / Q000276:immunology; D016399:Lymphoma, T-Cell / Q000276:immunology*; D051379:Mice; D009362:Neoplasm Metastasis / Q000276:immunology; D037342:Pertussis Toxin; D011994:Recombinant Proteins / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology*; D010566:Virulence Factors, Bordetella / Q000276:immunology*
D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D010566:Virulence Factors, Bordetella; D037342:Pertussis Toxin