Treatment with human recombinant leukocyte interferons inhibitsin vitro invasive ability of human lung carcinoma cells

Abstract

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.

Inhibition of p-STAT3 Enhances IFN-α Efficacy against Metastatic Melanoma in a Murine Model

“…In contrast, no large cooperative-group trials have shown significant prolongation of survival with IFN-α for inoperable stage IV melanoma and especially for those with the central nervous system (CNS) melanoma and metastasis. IFN-α is known to have powerful effects on immune cells, including enhancing NK cell tumor cytotoxicity (3), dendritic cell maturation, Th1 skewing, enhancement of T cell survival, inducing immunological memory (4), and inhibiting the invasive ability of cancer cells (5). Therapeutic strategies using IFN-α in melanoma patients with LMD have included the direct intraventricular administration of IFN-α, which resulted in the clearance of malignant cells in the cerebrospinal fluid CSF (6) but was confounded by significant and sustained neurotoxicity (7).…”

In vitro Comparative Study of the Antitumor Effects of Human Interferon‐α, β and γ on the Growth and Invasive Potential of Human Melanoma Cells

“…Interferons (IFNs) exert antiviral and antitumoral activity by suppressing either proliferative or metastatic potential of different types of tumor cells (1,2). IFNs are also able to affect normal cellular processes such as proliferation, differentiation, and expression of cell surface receptors.…”

Recombinant interferon alpha and gamma modulate the invasive potential of human melanoma in vitro

“…Several studies report either stimulatory or inhibitory effects of interferons on tumor cell invasion and metastasis (Siegal et al, 1982;Brunda et al, 1984;Nishimura et al, 1985;Lollini et al, 1987;Balkwill, 1987, 1989). In other studies, a pre-treatment of malignant or transformed cells with interferons has inhibited invasion in vitro (Ravine and Ledinko, 1986;Melchiori et al, 1987). Our results, however, show that interferons alpha and gamma enhanced the invasive capacity of human melanoma cells in vitro after a short pre-treatment.…”

“…In addition to their antiviral and antitumoral effects, interferons are able to affect such cellular processes as proliferation, differentiation and cell surface receptors (Pestka et al, 1987). Several in vitro and in vivo studies show that interferons either enhance or suppress the invasive and metastatic potential of a number of different tumor cells (Siegal et al, 1982;Brunda et al, 1984;Nishimura et al, 1985; Balkwill, 1987, 1989;Ravine and Ledinko, 1986;Lollini et al, 1987;Melchiori et al, 1987). However, it is not known how these drugs affect the distinct steps of the metastatic cascade.Metastasis is a multi-step process involving a variety of interactions between tumor cells and the host.…”