期刊
ONCOLOGY REPORTS
卷 40, 期 2, 页码 1185-1195出版社
SPANDIDOS PUBL LTD
DOI: 10.3892/or.2018.6500
关键词
cancer-associated fibroblasts; gastric cancer; hepatocyte growth factor; angiogenesis
类别
资金
- National Science Foundation of China [81672327, 81502013, 81602411]
- Program of Shanghai Academic/Technology Research Leader [17XD1402600]
- Program for Outstanding Medical Academic Leader
- Development Grant for Clinical Trial [SHDC12017X06]
- SCORE Foundation [Y-MX2015-078]
- Shanghai Municipal Commission of Health and Family Planning [20154Y496]
- Shanghai Municipal Education Commission-Gaofeng Clinical Medicine Grant Support [20161410]
Cancer-associated fibroblasts (CAFs) are predominate cells in tumor stroma and play a key role in tumor progression. Hepatocyte growth factor (HGF) is a cytokine mainly derived from fibroblasts. In the present study, we reported that HGF significantly promoted angiogenesis of human umbilical vein endothelial cells (HUVECs) and vasculogenic mimicry (VM) formation of gastric cancer cells, respectively, by increasing cell proliferation and migration. In addition, mosaic vessels formed by HUVECs and gastric cancer cells were also increased with treatment of recombinant human HGF and conditioned medium from CAFs. The opposite results were achieved in HGF-neutralized groups. In accordance with these observations, we determined that phosphorylation of AKT and ERK1/2 were upregulated in HUVECs and gastric cancer cells with HGF treatment and co-culture with CAFs. Both AKT inhibitor LY294002 and ERK1/2 inhibitor U0126 reduced the ability of angiogenesis and VM formation, as well as mosaic vessel formation induced by HGF. Gene Set Enrichment Analysis and correlation analysis were performed to confirm our findings. In conclusion, CAF-derived HGF promotes angiogenesis, VM and mosaic vessel formation via PI3K/AKT and ERK1/2 signaling in gastric cancer and HGF may serve as a potential therapeutic target for cancer anti-vascular treatment.
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