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Gastric Cancer
Published in: Gastric Cancer 4/2018

01-07-2018 | Original Article

Kallistatin inhibits lymphangiogenesis and lymphatic metastasis of gastric cancer by downregulating VEGF-C expression and secretion

Authors: Caiqi Ma, Chuanghua Luo, Haofan Yin, Yang Zhang, Wenjun Xiong, Ting Zhang, Tianxiao Gao, Xi Wang, Di Che, Zhenzhen Fang, Lei Li, Jinye Xie, Mao Huang, Liuqing Zhu, Ping Jiang, Weiwei Qi, Ti Zhou, Zhonghan Yang, Wei Wang, Jianxing Ma, Guoquan Gao, Xia Yang

Published in: Gastric Cancer | Issue 4/2018

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Abstract

Background

Tumor-induced lymphangiogenesis and lymphatic metastasis are predominant during the metastasis of many types of cancers. However, the endogenous inhibitors that counterbalance the lymphangiogenesis and lymphatic metastasis of tumors have not been well evaluated. Kallistatin has been recognized as an endogenous angiogenesis inhibitor.

Methods and results

Our recent study showed for the first time that the lymphatic vessel density (LVD) was reduced in lung and stomach sections from kallistatin-overexpressing transgenic mice. Kallistatin expresses anti-lymphangiogenic activity by inhibiting the proliferation, migration, and tube formation of human lymphatic endothelial cells (hLECs). Therefore, the present study focuses on the relationships of changes in kallistatin expression with the lymphangiogenesis and lymphatic metastasis of gastric cancer and its underlying mechanisms. Our results revealed that the expression of kallistatin in cancer tissues, metastatic lymph nodes, and plasma of gastric cancer patients was significantly downregulated and that the plasma level of kallistatin was negatively associated with the phase of lymph node metastasis. Furthermore, treatment with kallistatin recombinant protein decreased LVD and lymph node metastases in the implanted gastric xenograft tumors of nude mice. Mechanically, kallistatin suppressed the lymphangiogenesis and lymphatic metastasis by downregulating VEGF-C expression and secretion through the LRP6/IKK/IҡB/NF-ҡB signaling pathway in gastric cancer cells.

Conclusions

These findings demonstrated that kallistatin functions as an endogenous lymphangiogenesis inhibitor and has an important part in the lymphatic metastasis of gastric cancer.
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Metadata
Title
Kallistatin inhibits lymphangiogenesis and lymphatic metastasis of gastric cancer by downregulating VEGF-C expression and secretion
Authors
Caiqi Ma
Chuanghua Luo
Haofan Yin
Yang Zhang
Wenjun Xiong
Ting Zhang
Tianxiao Gao
Xi Wang
Di Che
Zhenzhen Fang
Lei Li
Jinye Xie
Mao Huang
Liuqing Zhu
Ping Jiang
Weiwei Qi
Ti Zhou
Zhonghan Yang
Wei Wang
Jianxing Ma
Guoquan Gao
Xia Yang
Publication date
01-07-2018
Publisher
Springer Japan
Published in
Gastric Cancer / Issue 4/2018
Print ISSN: 1436-3291
Electronic ISSN: 1436-3305
DOI
https://doi.org/10.1007/s10120-017-0787-5

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WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

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