The Combination of IFN-α2 and IFN-α8 Exhibits Synergistic Antiproliferative Activity on Renal Cell Carcinoma (RCC) Cell Lines Through Increased Binding Affinity for IFNAR-2.

Autor: Tadao Tanimoto, Shigeto Yamamoto, Madoka Taniai, Mutsuko Taniguchi, Harumi Ariyasu, Chie Ushio, Miho Aga, Yohei Mukai, Yasuo Tsutsumi, Toshio Ariyasu, Tsunetaka Ohta, Shigeharu Fukuda
Předmět:
Zdroj: Journal of Interferon & Cytokine Research; Jun2007, Vol. 27 Issue 6, p517-524, 8p
Abstrakt: Although there are at least 13 interferon-α(IFN-α) subtypes in humans, interactions between the subtypes remain unknown. To understand IFN-αinteractions, we examined the antiproliferative activities and the receptor binding affinities of different combinations of IFN-α2 and IFN-α8 using six renal cell carcinoma (RCC) cell lines. Although IFN-α8 was the more potent subtype, synergistic and antagonistic antiproliferative effects were also observed in certain combinations of IFN-α2 and IFN-α8. To analyze the interactions between IFN-α2 and IFN-α8, the receptor-binding kinetics of different combinations of IFN-α2 and IFN- α8 to the IFN-αreceptors, IFNAR-1 or IFNAR-2, were measured using a surface plasmon resonance-based biosensor. Unexpectedly, the receptor binding kinetics to IFNAR-2 but not to IFNAR-1 were mutually related to antiproliferative activity and increase in the binding speed (Ka) for IFNAR-2. Moreover, we observed the increased fluorescence intensity (FI) of biotin-labeled IFN-α8 to IFNAR-2 by receptor binding inhibition assay with unlabeled IFN-α2 but not the other combinations. These findings indicate that the binding manner of IFN-α8 for IFNAR-2 is different from that of IFN-α2, suggesting that binding of IFN-α8 rather than binding of IFN-α2 to IFNAR-2 leads to activation and subsequent antiproliferative activity despite the same antiviral activity in RCC. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index