Modulation of Interferon Receptor Expression during Combination βser-Interferon and γ-Interferon Treatment of Human Colon Carcinoma Cells

Joan H. Schiller, Sarah M. Bushmeyer, Frank J. Ruzicka, Gerald L. Princler, Connie R. Faltynek, Ernest C. Borden

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

Combination treatment of SKCOl human colon carcinoma cells with βser-interferon (IFN-γser) and γ-interferon (IFN-γ) results in a synergistic antiproliferative effect. The role of IFN-fte, and IFN-7 receptor modulation was investigated as a possible mechanism for this response. IFN-7 (0.05–50 ng/ml) pretreatment of SKCOl cells for 24 h decreased specific binding of 125I-IFN-βser, by 35–60%. Scatchard analysis of binding data obtained following 24-h treatment with 5 ng/ml IFN-7 showed that this reduction in binding was due to a decreased receptor affinity (control cells, Kd = 46 ± 1.6 pM; IFN-γ-treated cells, Kd = 106 ± 6 pM, n = 2) rather than a significant change in receptor number (receptor number/ control cell = 1214 ± 471, receptor number/IFN-7 treated cell = 1118 ± 153, #1 = 2). In contrast, pretreatment of SKCOl cells with IFN-A., (5 ng/ml) resulted in slight (10–35%) increases in, 25I-IFN-γ-specific binding. Scatchard analysis of binding data obtained following 24-h treatment with 5 ng/ml IFN-βser showed a decrease in binding affinity (control cells, K4 = 28 ± 7 pm; IFN-βser-treated cells, K4 = 38 ± 7 pM, n = 2) and a 32% increase in IFN-7 receptor sites (receptor number/control cell = 4257 ± 464, receptor number/IFN-βser-treated cell = 5570 ± 730; n = 2). 125I-IFN-7 internalization studies performed at 37°C confirmed the cell surface binding assays; IFN-βser-treated cells internalized 30–50% more labeled IFN-7 than untreated cells. However, it is unlikely that differences in binding and internalization of this magnitude play a primary role in the synergistic antiproliferative effect of IFN-7 with IFN-ftc in SKCOl cells. Biochemical modulation at sites distal to the ligand receptor interaction should be investigated.

Original languageEnglish (US)
Pages (from-to)26-31
Number of pages6
JournalCancer research
Volume50
Issue number1
StatePublished - Jan 1 1990

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Schiller, J. H., Bushmeyer, S. M., Ruzicka, F. J., Princler, G. L., Faltynek, C. R., & Borden, E. C. (1990). Modulation of Interferon Receptor Expression during Combination βser-Interferon and γ-Interferon Treatment of Human Colon Carcinoma Cells. Cancer research, 50(1), 26-31.