Growth regulation of melanoma cells by interferon and (2'-5')oligoadenylate synthetase.

Abstract

We report that endogenous, as well as exogenous, interferon (IFN) regulates the growth of human melanoma cells in culture. When antibodies directed against human fibroblast IFN were incorporated into the media of high-density cells stimulated to proliferate with serum, the cells entered the cell cycle earlier than did the controls. In investigating the biochemical basis for this finding, we have found that there is an inverse relationship between the (2'-5')oligoadenylate synthetase levels and the percentage of cells in S in untreated cultures. Upon IFN treatment, the relationship is obliterated and (2'-5')oligoadenylate synthetase levels increase throughout all phases of the cell cycle. This increase in enzyme levels correlates well with the decreased probability of the IFN-treated cells to cycle. These findings suggest a biological role for IFN as a negative growth factor for cells in culture.

IFN-Induced Protein with Tetratricopeptide Repeats 2 Inhibits Migration Activity and Increases Survival of Oral Squamous Cell Carcinoma

“…IFNs have been evaluated as therapeutic agents against several malignancies, including melanoma and chronic myelogenous leukemia (38,39). In this study, we showed that IFIT2 expression was increased and cell migratory ability was inhibited at 500 units/mL of IFN-h in OC3 and OECM-1 cells that expressed relatively low levels of IFIT2.…”

Activation of 2',5'-oligoadenylate synthetase activity on induction of HL-60 leukemia cell differentiation.

“…Their potential role as naturally occurring negative growth factors is supported by evidence that IFNs are released in an autocrine manner upon mitogenic stimulation of human fibroblasts (20,21,40) and other cell types (4,5).…”

“…Enzyme assays were for 16 h at 30°C in 10 ,ul and contained 10 ,uCi of [ct-32PIATP (Dupont, NEN Research Products, Boston, Mass.) at a final concentration of 3.5 mM, 20 mM N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid (HEPES) (pH 7.5), 120 mM KCl, 5 mM Mg(CH2COOH)2, 7 mM f3-mercaptoethanol, and 10% glycerol (29). Samples were treated with 1 U of alkaline phosphatase and analyzed by high-pressure liquid chromatography (HPLC) using an ODS-18 column (Whatman, Inc., Clifton, N.J.) and a 20-min linear gradient of 4 mM KHPO4 (pH 6.8) to 20% methanol at 1.5 ml/min (1).…”

“…Cells were passaged weekly and screened for mycoplasma contamination; only cells between passage 25 and 50 were used. For growth in serum-free defined medium, cells were washed twice and resuspended in RPMI 1640 medium with insulin and transferrin (at 5 ,ug/ml for both) (Sigma Chemical Co., St. Louis, Mo.). Sheep antiserum against human alpha interferon (IFN-a) (G-026-502-568) or human IFN-,B (G-028-501-568), rabbit antiserum against human gamma interferon (IFN-y) (G-034-501-565), and the corresponding control antisera were obtained from the Research Resource Branch, National Institute of Allergy and Infectious Diseases, Bethesda, Md.…”

Induction of Oligo-2',5'-adenylate Synthetase in Human Lymphoid Cells Treated with 5-Azacytosine and 5-Iododeoxyuridine

“…Furthermore, it has been reported that the enzyme is induced by some other compounds including hormones (Itkes et al, 1982;Oikarinen, 1982;Besancon et al, 1981;Orlic et al, 1982;Krishnan & Baglioni, 1980). Oligo-2',5'-adenylate (2-5A) formed by this enzyme has several functions such as in cell growth regulation (Creasey et al, 1983;Jacobsen et al, 1983;Kimchi et al, 1979;Krishnan & Baglioni, 1980;Leanderson et al, 1982;Smekens et al, 1983), in cell differentiation (Schmidt et al, 1984) and in degradation of cellular or viral mRNA through the activation of endoribonuclease L (Ball, 1982;Jacobsen et al, 1983;Oikarinen, 1982).…”