Treatment with human recombinant leukocyte interferons inhibits in vitro invasive ability of human lung carcinoma cells.
The effects of treatment of human lung carcinoma cell line A 549 with recombinant DNA-derived human leukocyte interferons A (rIFN-alpha A) or D (rIFN-alpha D), and human lymphoblastoid interferon (Wellferon) on in vitro cell invasion were investigated in a quantitative invasion assay using human amnion. The A 549 cells treated with IFN for one day were incubated on the denuded basement membrane of the amnion in the absence of IFN, and cells which penetrated the full thickness of the connective tissue barrier were measured after 4 days. A dose-dependent inhibition of cell invasion was produced by the recombinant IFNs. The one day treatment of cells with 2.4 X 10(3) to 1.8 X 10(4) units/ml of rIFN-alpha A resulted in a 60-80 per cent inhibition of invasiveness compared to untreated cells. After a one day exposure of cells to 2.2 X 10(4) units/ml of rIFN-alpha D, cell invasion was reduced by approximately 70 per cent; a concentration of 4.4 X 10(3) units/ml had no apparent effect. Similar treatment with lymphoblastoid IFN (6 X 10(4) units/ml) had no significant effect on cell invasion. Accompanying the one day exposure to rIFN-alpha A (1.8 X 10(4) units/ml) or rIFN-alpha D (2.2 X 10(4) units/ml), (2',5') oligo (A) synthetase activity was induced approximately 20-fold; a 4-fold induction of enzyme activity was found in cells exposed to lymphoblastoid IFN (6 X 10(4) units/ml). After exposure of A 549 cells to the three IFNs at these concentrations, no significant alteration of the ability of the cells to attach to the basement membrane was found. Moreover, none of the one day IFN treatment regimens were cytocidal, and cell proliferation ability was not affected. This model system may be useful for investigating anti-invasive activity of other IFN types and subtypes.
D015088:2',5'-Oligoadenylate Synthetase / Q000378:metabolism; D000650:Amnion; D002277:Carcinoma / Q000188:drug therapy / Q000473:pathology*; D002460:Cell Line; D006801:Humans; D066298:In Vitro Techniques; D007370:Interferon Type I / Q000627:therapeutic use; D007372:Interferons / Q000627:therapeutic use*; D007962:Leukocytes; D008175:Lung Neoplasms / Q000188:drug therapy / Q000473:pathology*; D009361:Neoplasm Invasiveness; D011994:Recombinant Proteins / Q000627:therapeutic use
D007370:Interferon Type I; D011994:Recombinant Proteins; D007372:Interferons; D015088:2',5'-Oligoadenylate Synthetase