Kallistatin exerts anti-lymphangiogenic effects by inhibiting lymphatic endothelial cell proliferation, migration and tube formation.
Kallistatin exerts anti-lymphangiogenic effects by inhibiting lymphatic endothelial cell proliferation, migration and tube formation.
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卡利他汀通过抑制淋巴管内皮细胞增殖、迁移和管形成来发挥抗淋巴管生成作用
DOI：
10.3892/ijo.2017.3972
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发表时间：
2017-06
影响因子：
5.2
通讯作者：
Gao G
中科院分区：
文献类型：
--
作者：
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被认为是一种内源性血管生成抑制剂。然而，其对淋巴管内皮细胞和淋巴管生成的影响仍然知之甚少。在各种类型的肿瘤中，淋巴管生成通过淋巴管系统参与肿瘤转移。本研究的目的是探讨激肽对淋巴管生成的影响及其作用机制。重组或过表达的kallistatin可抑制人淋巴管内皮细胞（hLECs）的增殖、迁移和管腔形成，并诱导hLECs凋亡。此外，我们的研究结果表明，淋巴管密度（LVD）减少肺和胃切片从激肽过表达转基因小鼠。卡利斯他汀重组蛋白治疗可降低裸小鼠胃移植瘤的LVD。据我们所知，本研究是第一个证明，激肽具有抗淋巴管生成活性，在体外和体内。此外，kallistatin通过减少ERK和Akt的磷酸化，分别抑制hLEC的增殖和迁移。这些结果表明，激肽可能是一个有前途的代理，可用于抑制肿瘤转移，抑制血管生成和淋巴管生成。
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.