Cross-talk mechanism between endothelial cells and hepatocellular carcinoma cells via growth factors and integrin pathway promotes tumor angiogenesis and cell migration.

Cross-talk mechanism between endothelial cells and hepatocellular carcinoma cells via growth factors and integrin pathway promotes tumor angiogenesis and cell migration.
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内皮细胞与肝癌细胞通过生长因子和整合素通路的串扰机制促进肿瘤血管生成和细胞迁移

DOI:
10.18632/oncotarget.18632
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发表时间:
2017-09-19
期刊:
影响因子:
--
通讯作者:
Liu X
Liu X
中科院分区:
其他
文献类型:
--
作者:
Feng T;Yu H;Xia Q;Ma Y;Yin H;Shen Y;Liu X

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肿瘤血管生成在肝细胞癌的发生、发展和转移中起核心作用。肿瘤细胞分泌血管生成因子募集血管内皮细胞,维持肿瘤血管网络,促进肿瘤细胞的迁移和侵袭。因此,血管内皮细胞和癌细胞之间的串扰是至关重要的,然而,对于这些细胞相互作用的串扰机制还知之甚少。本研究通过更换培养基对血管内皮细胞EA.hy926细胞和肝细胞癌HepG2细胞的增殖、迁移、侵袭和管状形成进行了研究。研究整合素诱导的与细胞迁移相关的信号通路的时间依赖性差异。结果表明,HepG2细胞通过释放生长因子显著增强EA.hy926细胞的增殖和迁移能力以及管状细胞的形成。此外,EA.hy926细胞还能促进HepG2细胞的增殖、迁移和侵袭能力。进一步的分析表明,在条件培养液中,两种细胞的整合素-FAK-Rho GTP酶信号事件都被激活,并且两种细胞系的信号分子在1h内表现出不同的时间依赖性表达。这些发现揭示了内皮细胞和肝癌细胞之间的串扰机制,有望为肝细胞癌的防治找到新的思路。
Tumor angiogenesis plays a central role in the development and metastasis of hepatocellular carcinoma. Cancer cells secrete angiogenic factors to recruit vascular endothelial cells and sustain tumor vascular networks, which facilitate the migration and invasion of cancer cells. Therefore, the cross-talk between vascular endothelial cells and cancer cells is vitally necessary, however, little is known about the cross-talk mechanism of these cells interaction. In the present study, the proliferation, migration, invasion and tube formation of vascular endothelial EA.hy926 cells and hepatocellular carcinoma HepG2 cells were studied by exchanging their culture medium. The time-dependent differences of integrins induced signaling pathway associated with cell migration were investigated. Our results showed that HepG2 cells markedly enhanced the proliferation and migration ability as well as the tube formation of EA.hy926 cells by releasing growth factors. Also, the EA.hy926 cells promoted the proliferation, migration and invasion ability of HepG2 cells. The further analysis demonstrated that the integrins-FAK-Rho GTPases signaling events in both of two cells was activated under conditioned medium, and the signaling molecules in two cell lines showed a different time-dependent expression within 1h. These findings reveal the cross-talk mechanism between the endothelial cells and hepatocellular carcinoma cells, which were expected to find out new ideas for the prevention and treatment of hepatocellular carcinoma.
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