Journal
CANCER LETTERS
Volume 385, Issue -, Pages 28-38Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2016.10.043
Keywords
CXCL1; Integrin beta 1; Lymphatic endothelial cells; Gastric cancer
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Funding
- National Natural Science Foundation of China [81272637, 81472260]
- Natural Science Foundation of Guangdong Province [52013020012724, 2015A030313053]
- Science and Technology Program of Guangzhou [201510010146]
- Young Teachers Cultivation Program of Sun Yat-sen University [15ykpy17]
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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.
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