CXCL1 from tumor-associated lymphatic endothelial cells drives gastric cancer cell into lymphatic system via activating integrin β1/FAK/AKT signaling
CXCL1 from tumor-associated lymphatic endothelial cells drives gastric cancer cell into lymphatic system via activating integrin β1/FAK/AKT signaling
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DOI：
10.1016/j.canlet.2016.10.043
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发表时间：
2017-01-28
期刊：
影响因子：
9.7
通讯作者：
He, Yulong
中科院分区：
文献类型：
--
作者：
Wang, Zhixiong;Wang, Zhao;He, Yulong
肿瘤微环境中淋巴管内皮细胞（LECs）与肿瘤细胞之间的相互作用在肿瘤转移中起着至关重要的作用。我们前期的研究表明淋巴管内皮细胞趋化因子配体1（C-X-C motif ligand 1，CXCL 1）刺激胃癌的转移。然而，其机制尚不清楚。在此，我们成功地分离肿瘤相关的LEC（T-LEC）和正常的LEC（N-LEC）从临床样品中的磁激活细胞分选系统（MACS），并证明CXCL 1表达在T-LEC中升高相比，N-LEC在原位和体外。此外，我们证明了T-LEC分泌的CXCL 1通过上调整合素β 1、MMP 2和MMP 9促进胃癌细胞的迁移、侵袭和粘附。此外，CXCL 1通过激活整合素β 1-FAK-AKT信号传导诱导MMP 2/9表达。在动物模型中，CXCL 1在LEC中过表达增加胃癌的淋巴结转移。结论：T-LECs中CXCL 1表达上调，T-LECs分泌的CXCL 1通过整合素β 1/FAK/AKT信号通路促进胃癌淋巴结转移，进而导致MMP 2和MMP 9的表达。因此，在T-LEC中产生的CXCL 1代表了治疗胃癌的潜在有希望的靶点。(C)2016爱思唯尔爱尔兰有限公司版权所有。
Crosstalk between lymphatic endothelial cells (LECs) and tumor cells in the tumor microenvironment plays a crucial role in tumor metastasis. Our previous study indicated chemokine (C-X-C motif) ligand 1 (CXCL1) from LECs stimulates the metastasis of gastric cancer. However, the mechanism is still unclear. Here, we successfully isolated tumor-associated LECs (T-LECs) and normal LECs (N-LECs) from clinical samples by magnetic-activated cell sorting system (MACS) and proved that CXCL1 expression was elevated in T-LECs compared with N-LECs in situ and vitro. Besides, we demonstrated that CXCL1 secreted by T-LECs promoted the migration, invasion, and adhesion of gastric cancer cells by upregulating integrin beta 1, MMP2, and MMP9. Furthermore, CXCL1 induced MMP2/9 expression by activating integrin beta 1-FAK-AKT signaling. In the animal model, CXCL1 overexpressed in LECs increased the lymph node metastasis of gastric cancer. In conclusion, CXCL1 expression in T-LECs was upregulated, and CXCL1 secreted by T-LECs promoted the lymph node metastasis of gastric cancer through integrin beta 1/FAK/AKT signaling, leading to MMP2 and MMP9 expression. Therefore, CXCL1 produced in T-LECs represents a potentially promising target for treating gastric cancer. (C) 2016 Elsevier Ireland Ltd. All rights reserved.