Molecules and Cells

Korean Society for Molecular and Cellular Biology (한국분자세포생물학회)
권호 표지
DOI QR코드

DOI QR Code

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)
  • Received : 2016.02.23
  • Accepted : 2016.05.27
  • Published : 2016.07.31
Download PDF
⟨ Previous Next ⟩

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

References

  1. Atkins, M.B., Robertson, M.J., Gordon, M., Lotze, M.T., DeCoste, M., DuBois, J.S., Ritz, J., Sandler, A.B., Edington, H.D., Garzone, P.D., et al. (1997). Phase I evaluation of intravenous recombinant human interleukin 12 in patients with advanced malignancies. Clin. Cancer. Res. 3, 409-417.
  2. Batts, T.D., Machado, H.L., Zhang, Y., Creighton, C.J., Li, Y., and Rosen, J.M. (2011). Stem cell antigen-1 (sca-1) regulates mammary tumor development and cell migration. PLoS One 6, e27841. https://doi.org/10.1371/journal.pone.0027841
  3. Benchetrit, F., Ciree, A., Vives, V., Warnier, G., Gey, A., Sautes-Fridman, C., Fossiez, F., Haicheur, N., Fridman, W.H., and Tartour, E. (2002). Interleukin-17 inhibits tumor cell growth by means of a T-cell-dependent mechanism. Blood 99, 2114-2121. https://doi.org/10.1182/blood.V99.6.2114
  4. Car, B.D., Eng, V.M., Lipman, J.M., and Anderson, T.D. (1999). The toxicology of interleukin-12: a review. Toxicol. Pathol. 27, 58-63. https://doi.org/10.1177/019262339902700112
  5. Chiricozzi, A., Nograles, K.E., Johnson-Huang, L.M., Fuentes-Duculan, J., Cardinale, I., Bonifacio, K.M., Gulati, N., Mitsui, H., Guttman-Yassky, E., Suarez-Farinas, M., et al. (2014). IL-17 induces an expanded range of downstream genes in reconstituted human epidermis model. PLoS One 9, e90284. https://doi.org/10.1371/journal.pone.0090284
  6. Hirahara, N., Nio, Y., Sasaki, S., Minari, Y., Takamura, M., Iguchi, C., Dong, M., Yamasawa, K., and Tamura, K. (2001). Inoculation of human interleukin-17 gene-transfected Meth-A fibrosarcoma cells induces T cell-dependent tumor-specific immunity in mice. Oncology 61, 79-89. https://doi.org/10.1159/000055357
  7. Horiuchi, T., Mitoma, H., Harashima, S., Tsukamoto, H., and Shimoda, T. (2010). Transmembrane TNF-alpha: structure, function and interaction with anti-TNF agents. Rheumatology (Oxford) 49, 1215-1228. https://doi.org/10.1093/rheumatology/keq031
  8. Hyun, Y.S., Han, D.S., Lee, A.R., Eun, C.S., Youn, J., and Kim, H.Y. (2012). Role of IL-17A in the development of colitis-associated cancer. Carcinogenesis 33, 931-936. https://doi.org/10.1093/carcin/bgs106
  9. Ji, J., Li, J., Holmes, L.M., Burgin, K.E., Yu, X., Wagner, T.E., and Wei, Y. (2002). Glycoinositol phospholipid-anchored interleukin 2 but not secreted interleukin 2 inhibits melanoma tumor growth in mice. Mol. Cancer Ther. 1, 1019-1024.
  10. Kim, Y.S., Sonn, C.H., Paik, S.G., and Bothwell, A.L. (2000). Tumor cells expressing membrane-bound form of IL-4 induce antitumor immunity. Gene Ther. 7, 837-843. https://doi.org/10.1038/sj.gt.3301175
  11. Kryczek, I., Wei, S., Szeliga, W., Vatan, L., and Zou, W. (2009). Endogenous IL-17 contributes to reduced tumor growth and metastasis. Blood 114, 357-359. https://doi.org/10.1182/blood-2008-09-177360
  12. Kung, A.L., Sherwood, S.W., and Schimke, R.T. (1990). Cell linespecific differences in the control of cell cycle progression in the absence of mitosis. Proc. Natl. Acad. Sci. USA 87, 9553-9557. https://doi.org/10.1073/pnas.87.24.9553
  13. Leonard, J.P., Sherman, M.L., Fisher, G.L., Buchanan, L.J., Larsen, G., Atkins, M.B., Sosman, J.A., Dutcher, J.P., Vogelzang, N.J., and Ryan, J.L. (1997). Effects of single-dose interleukin-12 exposure on interleukin-12-associated toxicity and interferongamma production. Blood 90, 2541-2548.
  14. Lim, H.Y., Ju, H.Y., Chung, H.Y., and Kim, Y.S. (2010). Anti-tumor effects of a tumor cell vaccine expressing a membrane-bound form of the IL-12 p35 subunit. Cancer Biol. Ther. 10, 336-343. https://doi.org/10.4161/cbt.10.4.12310
  15. Marr, R.A., Addison, C.L., Snider, D., Muller, W.J., Gauldie, J., and Graham, F.L. (1997). Tumour immunotherapy using an adenoviral vector expressing a membrane-bound mutant of murine TNF alpha. Gene Ther. 4, 1181-1188. https://doi.org/10.1038/sj.gt.3300528
  16. Miyahara, Y., Odunsi, K., Chen, W., Peng, G., Matsuzaki, J., and Wang, R.F. (2008). Generation and regulation of human CD4+ IL-17-producing T cells in ovarian cancer. Proc. Natl. Acad. Sci. USA 105, 15505-15510. https://doi.org/10.1073/pnas.0710686105
  17. Moseley, T.A., Haudenschild, D.R., Rose, L., and Reddi, A.H. (2003). Interleukin-17 family and IL-17 receptors. Cytokine Growth Factor Rev. 14, 155-174. https://doi.org/10.1016/S1359-6101(03)00002-9
  18. Numasaki, M., Fukushi, J., Ono, M., Narula, S.K., Zavodny, P.J., Kudo, T., Robbins, P.D., Tahara, H., and Lotze, M.T. (2003). Interleukin-17 promotes angiogenesis and tumor growth. Blood 101, 2620-2627. https://doi.org/10.1182/blood-2002-05-1461
  19. Puck, T.T., and Steffen, J. (1963). Life Cycle Analysis of Mammalian Cells. I. A method for localizing metabolic events within the life cycle, and its application to the action of colcemide and sublethal doses of X-irradiation. Biophys J. 3, 379-397. https://doi.org/10.1016/S0006-3495(63)86828-9
  20. Rieder, C.L., and Maiato, H. (2004). Stuck in division or passing through: what happens when cells cannot satisfy the spindle assembly checkpoint. Dev. Cell 7, 637-651. https://doi.org/10.1016/j.devcel.2004.09.002
  21. Rieder, C.L., and Palazzo, R.E. (1992). Colcemid and the mitotic cycle. J. Cell Sci. 102 ( Pt 3), 387-392.
  22. Rouvier, E., Luciani, M.F., Mattei, M.G., Denizot, F., and Golstein, P. (1993). CTLA-8, cloned from an activated T cell, bearing AU-rich messenger RNA instability sequences, and homologous to a herpesvirus saimiri gene. J. Immunol. 150, 5445-5456.
  23. Sfanos, K.S., Bruno, T.C., Maris, C.H., Xu, L., Thoburn, C.J., DeMarzo, A.M., Meeker, A.K., Isaacs, W.B., and Drake, C.G. (2008). Phenotypic analysis of prostate-infiltrating lymphocytes reveals TH17 and Treg skewing. Clin. Cancer Res. 14, 3254-3261. https://doi.org/10.1158/1078-0432.CCR-07-5164
  24. Soo Hoo, W., Lundeen, K.A., Kohrumel, J.R., Pham, N.L., Brostoff, S.W., Bartholomew, R.M., and Carlo, D.J. (1999). Tumor cell surface expression of granulocyte-macrophage colonystimulating factor elicits antitumor immunity and protects from tumor challenge in the P815 mouse mastocytoma tumor model. J. Immunol. 162, 7343-7349.
  25. Tartour, E., Fossiez, F., Joyeux, I., Galinha, A., Gey, A., Claret, E., Sastre-Garau, X., Couturier, J., Mosseri, V., Vives, V., et al. (1999). Interleukin 17, a T-cell-derived cytokine, promotes tumorigenicity of human cervical tumors in nude mice. Cancer Res. 59, 3698-3704.
  26. Upadhyay, G., Yin, Y., Yuan, H., Li, X., Derynck, R., and Glazer, R.I. (2011). Stem cell antigen-1 enhances tumorigenicity by disruption of growth differentiation factor-10 (GDF10)-dependent TGF-beta signaling. Proc. Natl. Acad. Sci. USA 108, 7820-7825. https://doi.org/10.1073/pnas.1103441108
  27. Wang, L., Yi, T., Kortylewski, M., Pardoll, D.M., Zeng, D., and Yu, H. (2009). IL-17 can promote tumor growth through an IL-6-Stat3 signaling pathway. J. Exp. Med. 206, 1457-1464. https://doi.org/10.1084/jem.20090207
  28. Wang, L., Yi, T., Zhang, W., Pardoll, D.M., and Yu, H. (2010). IL-17 enhances tumor development in carcinogen-induced skin cancer. Cancer Res. 70, 10112-10120. https://doi.org/10.1158/0008-5472.CAN-10-0775
  29. Weaver, C.T., Harrington, L.E., Mangan, P.R., Gavrieli, M., and Murphy, K.M. (2006). Th17: an effector CD4 T cell lineage with regulatory T cell ties. Immunity 24, 677-688. https://doi.org/10.1016/j.immuni.2006.06.002
  30. Weaver, C.T., Hatton, R.D., Mangan, P.R., and Harrington, L.E. (2007). IL-17 family cytokines and the expanding diversity of effector T cell lineages. Annu. Rev. Immunol. 25, 821-852. https://doi.org/10.1146/annurev.immunol.25.022106.141557
  31. Xin, L., Lawson, D.A., and Witte, O.N. (2005). The Sca-1 cell surface marker enriches for a prostate-regenerating cell subpopulation that can initiate prostate tumorigenesis. Proc. Natl. Acad. Sci. U S A 102, 6942-6947. https://doi.org/10.1073/pnas.0502320102
  32. Yao, Z., Timour, M., Painter, S., Fanslow, W., and Spriggs, M. (1996). Complete nucleotide sequence of the mouse CTLA8 gene. Gene 168, 223-225. https://doi.org/10.1016/0378-1119(95)00778-4

Cited by

  1. Ectopically Expressed Membrane-bound Form of IL-9 Exerts Immune-stimulatory Effect on CT26 Colon Carcinoma Cells vol.18, pp.1, 2018, https://doi.org/10.4110/in.2018.18.e12
  2. Cell-Based IL-15:IL-15Rα Secreting Vaccine as an Effective Therapy for CT26 Colon Cancer in Mice vol.42, pp.12, 2016, https://doi.org/10.14348/molcells.2019.0188
  3. The Role of Interleukins in Colorectal Cancer vol.16, pp.13, 2016, https://doi.org/10.7150/ijbs.46651
  4. Interplay between the Gut Microbiota and Inflammatory Mediators in the Development of Colorectal Cancer vol.13, pp.4, 2021, https://doi.org/10.3390/cancers13040734
  5. Rationalizing heptadecaphobia: TH17 cells and associated cytokines in cancer and metastasis vol.288, pp.24, 2021, https://doi.org/10.1111/febs.15711