CXCL1 from tumor-associated lymphatic endothelial cells drives gastric cancer cell into lymphatic system via activating integrin β1/FAK/AKT signaling. (28th January 2017)

• Record Type: Journal Article
• Authors: Wang, Zhixiong; Wang, Zhao; Li, Guanghua; Wu, Hui; Sun, Kaiyu; Chen, Jianhui; Feng, Yun; Chen, Chuangqi; Cai, Shirong; Xu, Jianbo; He, Yulong
• Is Part Of: Cancer letters. Volume 385(2017)
• Page Start: 28
• Page End: 38
• Publication Date: 2017-01-28
• Subjects: CXCL1 -- Integrin β1 -- Lymphatic endothelial cells -- Gastric cancer; LECs lymphatic endothelial cells -- T-LECs tumor-associated lymphatic endothelial cells -- N-LEC normal lymphatic endothelial cells -- CXCL1 chemokine (C-X-C motif) ligand 1 -- MMP2 matrix metalloproteinase 2 -- MMP9 matrix metalloproteinase 9 -- VEGF-C vascular endothelial growth factor-C -- HDLECs human dermal lymphatic endothelial cells -- GC gastric cancer -- CM condition medium; Cancer -- Periodicals; Neoplasms -- Periodicals; Cancer -- Périodiques; Electronic journals; 616.994
• DOI: 10.1016/j.canlet.2016.10.043
• Languages: English
• ISSNs: 0304-3835

Abstract

Abstract: 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 β1, MMP2, and MMP9. Furthermore, CXCL1 induced MMP2/9 expression by activating integrin β1-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 β1/FAK/AKT signaling, leading to MMP2 and MMP9 expression. Therefore, CXCL1 produced in T-LECs represents a potentially promising target for treating gastric cancer. Highlights: The expression of CXCL1 in T-LECs was elevated. T-LECs promoted the metastasis of gastric cancer by secreting CXCL1. CXCL1 from T-LECs promoted the lymphatic metastasis of gastric cancer by activating integrin β1/FAK/AKT signaling.