Open Access

Kallistatin exerts anti-lymphangiogenic effects by inhibiting lymphatic endothelial cell proliferation, migration and tube formation

  • Authors:
    • Caiqi Ma
    • Haofan Yin
    • Jun Zhong
    • Yang Zhang
    • Chuanghua Luo
    • Di Che
    • Zhenzhen Fang
    • Lei Li
    • Shuxing Qin
    • Jieying Liang
    • Weiwei Qi
    • Zhonghan Yang
    • Ti Zhou
    • Jianxing Ma
    • Xia Yang
    • Guoquan Gao
  • View Affiliations

  • Published online on: April 20, 2017     https://doi.org/10.3892/ijo.2017.3972
  • Pages: 2000-2010
  • Copyright: © Ma et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Kallistatin has been recognized as an endogenous angiogenic inhibitor. However, its effects on lymphatic endothelial cells and lymphangiogenesis remain poorly understood. Lymphangiogenesis is involved in tumor metastasis via the lymphatic vasculature in various types of tumors. The aim of this study was to investigate the effects of kallistatin on lymphangiogenesis and the mechanism of action involved. Treatment with kallistatin recombinant protein or overexpression of kallistatin inhibited the proliferation, migration and tube formation of human lymphatic endothelial cells (hLECs), and induced apoptosis of hLECs. Furthermore, our results showed that the lymphatic vessel density (LVD) was reduced in lung and stomach sections from kallistatin-overexpressing transgenic mice. Treatment with kallistatin recombinant protein decreased the LVD in the implanted gastric xenograft tumors of nude mice. To the best of our knowledge, the present study is the first to demonstrate that kallistatin possesses anti-lymphangiogenic activity in vitro and in vivo. Moreover, kallistatin inhibited proliferation and migration of hLECs by reducing the phosphorylation of ERK and Akt, respectively. These findings suggested that kallistatin may be a promising agent that could be used to suppress cancer metastasis by inhibiting both angiogenesis and lymphangiogenesis.
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June-2017
Volume 50 Issue 6

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Ma C, Yin H, Zhong J, Zhang Y, Luo C, Che D, Fang Z, Li L, Qin S, Liang J, Liang J, et al: Kallistatin exerts anti-lymphangiogenic effects by inhibiting lymphatic endothelial cell proliferation, migration and tube formation. Int J Oncol 50: 2000-2010, 2017
APA
Ma, C., Yin, H., Zhong, J., Zhang, Y., Luo, C., Che, D. ... Gao, G. (2017). Kallistatin exerts anti-lymphangiogenic effects by inhibiting lymphatic endothelial cell proliferation, migration and tube formation. International Journal of Oncology, 50, 2000-2010. https://doi.org/10.3892/ijo.2017.3972
MLA
Ma, C., Yin, H., Zhong, J., Zhang, Y., Luo, C., Che, D., Fang, Z., Li, L., Qin, S., Liang, J., Qi, W., Yang, Z., Zhou, T., Ma, J., Yang, X., Gao, G."Kallistatin exerts anti-lymphangiogenic effects by inhibiting lymphatic endothelial cell proliferation, migration and tube formation". International Journal of Oncology 50.6 (2017): 2000-2010.
Chicago
Ma, C., Yin, H., Zhong, J., Zhang, Y., Luo, C., Che, D., Fang, Z., Li, L., Qin, S., Liang, J., Qi, W., Yang, Z., Zhou, T., Ma, J., Yang, X., Gao, G."Kallistatin exerts anti-lymphangiogenic effects by inhibiting lymphatic endothelial cell proliferation, migration and tube formation". International Journal of Oncology 50, no. 6 (2017): 2000-2010. https://doi.org/10.3892/ijo.2017.3972