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http://dx.doi.org/10.14348/molcells.2020.0047

Interleukin-9 Inhibits Lung Metastasis of Melanoma through Stimulating Anti-Tumor M1 Macrophages  

Park, Sang Min (Department of Biochemistry, College of Natural Sciences, Chungnam National University)
Do-Thi, Van Anh (Department of Biochemistry, College of Natural Sciences, Chungnam National University)
Lee, Jie-Oh (Department of Life Sciences, POSTECH)
Lee, Hayyoung (Institute of Biotechnology, Chungnam National University)
Kim, Young Sang (Department of Biochemistry, College of Natural Sciences, Chungnam National University)
Publication Information
Molecules and Cells / v.43, no.5, 2020 , pp. 479-490 More about this Journal
Abstract
Interleukin-9 (IL-9) is well known for its role in allergic inflammation. For cancer, both pro- and anti-tumor effects of IL-9 were controversially reported, but the impact of IL-9 on tumor metastasis has not yet been clarified. In this study, IL-9 was expressed as a secretory form (sIL-9) and a membrane-bound form (mbIL-9) on B16F10 melanoma cells. The mbIL-9 was engineered as a chimeric protein with the transmembrane and cytoplasmic region of TNF-α. The effect of either mbIL-9 or sIL-9 expressing cells were analyzed on the metastasis capability of the cancer cells. After three weeks of tumor implantation into C57BL/6 mice through the tail vein, the number of tumor modules in lungs injected with IL-9 expressing B16F10 was 5-fold less than that of control groups. The percentages of CD4+ T cells, CD8+ T cells, NK cells, and M1 macrophages considerably increased in the lungs of the mice injected with IL-9 expressing cells. Among them, the M1 macrophage subset was the most significantly enhanced. Furthermore, peritoneal macrophages, which were stimulated with either sIL-9 or mbIL-9 expressing transfectant, exerted higher anti-tumor cytotoxicity compared with that of the mock control. The IL-9-stimulated peritoneal macrophages were highly polarized to M1 phenotype. Stimulation of RAW264.7 macrophages with sIL-9 or mbIL-9 expressing cells also significantly increased the cytotoxicity of those macrophages against wild-type B16F10 cells. These results clearly demonstrate that IL-9 can induce an anti-metastasis effect by enhancing the polarization and proliferation of M1 macrophages.
Keywords
anti-cancer; B16F10 melanoma; cytokine; immunotherapy; interleukin-9;
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