title: The Membrane-Bound Form of IL-17A Promotes the Growth and Tumorigenicity of Colon Cancer Cells.
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.
authors.affiliation: Department of Biochemistry, College of Natural Sciences, Chungnam National University, Daejeon 305-764, Korea.
authors.forename: Van Anh
authors.initials: VA
authors.lastname: Do Thi
authors.affiliation: Department of Biochemistry, College of Natural Sciences, Chungnam National University, Daejeon 305-764, Korea.
authors.forename: Sang Min
authors.initials: SM
authors.lastname: Park
authors.affiliation: Institute of Biotechnology, Chungnam National University, Daejeon 305-764, Korea.
authors.forename: Hayyoung
authors.initials: H
authors.lastname: Lee
authors.affiliation: Department of Biochemistry, College of Natural Sciences, Chungnam National University, Daejeon 305-764, Korea.
authors.forename: Young Sang
authors.initials: YS
authors.lastname: Kim
keywords: colon cancer; interleukin 17A; membrane-bound cytokine; pro-tumor; sca-1