title: Inhibition of lymphoma invasion and liver metastasis formation by pertussis toxin.
abstract: We have examined whether pertussis toxin, an agent known to inhibit entry of normal lymphocytes into tissues, affects invasion and metastasis formation by malignant lymphoma and T-cell hybridoma cells. The toxin reduced invasion in vitro in hepatocyte cultures to 20% of control values. Inhibition was maximal after pretreatment for 2 h with approximately 100 ng/ml. The effect of pretreatment with 1 to 5 micrograms toxin/ml for 4 h persisted for at least 5 days, despite a more than 100-fold increase in cell number. The proliferation rate was not affected. Liver metastasis formation after tail vein injection of TAM2D2 T-cell hybridoma cells in syngeneic AKR mice, measured as liver weight, was reduced to 10 to 25% of controls after pretreatment of the cells for 4 h with 1 microgram pertussis toxin/ml. Metastasis to kidneys, ovaries, and lymph nodes was not, or less evidently, affected. With MB6A lymphosarcoma cells no effect was seen after treatment with 1 microgram/ml, but a significant reduction of the liver tumor burden to approximately 50% of controls was achieved by treatment with at least 5 micrograms toxin/ml. Spleen metastasis by MB6A cells was not affected. These results provide evidence for a similarity in invasion mechanisms of normal and malignant lymphoid cells, and they suggest that invasiveness is an important factor in the formation of lymphoma metastases, particularly in the liver.
mesh_terms: D000818:Animals; D002460:Cell Line; D008113:Liver Neoplasms / Q000556:secondary*; D008223:Lymphoma / Q000188:drug therapy* / Q000556:secondary; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D009361:Neoplasm Invasiveness; D037342:Pertussis Toxin; D010566:Virulence Factors, Bordetella / Q000627:therapeutic use*
chemical_list: D010566:Virulence Factors, Bordetella; D037342:Pertussis Toxin