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 language||English (US)|
|Number of pages||6|
|State||Published - Jan 1 1990|
ASJC Scopus subject areas
- Cancer Research