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http://dx.doi.org/10.14348/molcells.2016.0048

The Membrane-Bound Form of IL-17A Promotes the Growth and Tumorigenicity of Colon Cancer Cells  

Thi, Van Anh Do (Department of Biochemistry, College of Natural Sciences, Chungnam National University)
Park, Sang Min (Department of Biochemistry, College of Natural Sciences, Chungnam National University)
Lee, Hayyoung (Institute of Biotechnology, Chungnam National University)
Kim, Young Sang (Department of Biochemistry, College of Natural Sciences, Chungnam National University)
Abstract
Interleukin-17A is a member of the IL-17 family, and is known as CTLA8 in the mouse. It is produced by T lymphocytes and NK cells and has proinflammatory roles, inducing cytokine and chemokine production. However, its role in tumor biology remains controversial. We investigated the effects of locally produced IL-17A by transferring the gene encoding it into CT26 colon cancer cells, either in a secretory or a membrane-bound form. Expression of the membrane-bound form on CT26 cells dramatically enhanced their proliferation in vitro. The enhanced growth was shown to be due to an increased rate of cell cycle progression: after synchronizing cells by adding and withdrawing colcemid, the rate of cell cycle progression in the cells expressing the membrane-bound form of IL-17A was much faster than that of the control cells. Both secretory and membrane-bound IL-17A induced the expression of Sca-1 in the cancer cells. When tumor clones were grafted into syngeneic BALB/c mice, the tumor clones expressing the membrane-bound form IL-17A grew rapidly; those expressing the secretory form also grew faster than the wild type CT26 cells, but slower than the clones expressing the membrane-bound form. These results indicate that IL-17A promotes tumorigenicity by enhancing cell cycle progression. This finding should be considered in treating tumors and immune-related diseases.
Keywords
colon cancer; interleukin 17A; membrane-bound cytokine; pro-tumor; sca-1;
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