HGF derived from cancer‑associated fibroblasts promotes vascularization in gastric cancer via PI3K/AKT and ERK1/2 signaling

  • Authors:
    • Xusheng Ding
    • Wenqi Xi
    • Jun Ji
    • Qu Cai
    • Jinling Jiang
    • Min Shi
    • Yingyan Yu
    • Zhenggang Zhu
    • Jun Zhang
  • View Affiliations

  • Published online on: June 18, 2018     https://doi.org/10.3892/or.2018.6500
  • Pages: 1185-1195
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Abstract

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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August-2018
Volume 40 Issue 2

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Ding X, Xi W, Ji J, Cai Q, Jiang J, Shi M, Yu Y, Zhu Z and Zhang J: HGF derived from cancer‑associated fibroblasts promotes vascularization in gastric cancer via PI3K/AKT and ERK1/2 signaling. Oncol Rep 40: 1185-1195, 2018
APA
Ding, X., Xi, W., Ji, J., Cai, Q., Jiang, J., Shi, M. ... Zhang, J. (2018). HGF derived from cancer‑associated fibroblasts promotes vascularization in gastric cancer via PI3K/AKT and ERK1/2 signaling. Oncology Reports, 40, 1185-1195. https://doi.org/10.3892/or.2018.6500
MLA
Ding, X., Xi, W., Ji, J., Cai, Q., Jiang, J., Shi, M., Yu, Y., Zhu, Z., Zhang, J."HGF derived from cancer‑associated fibroblasts promotes vascularization in gastric cancer via PI3K/AKT and ERK1/2 signaling". Oncology Reports 40.2 (2018): 1185-1195.
Chicago
Ding, X., Xi, W., Ji, J., Cai, Q., Jiang, J., Shi, M., Yu, Y., Zhu, Z., Zhang, J."HGF derived from cancer‑associated fibroblasts promotes vascularization in gastric cancer via PI3K/AKT and ERK1/2 signaling". Oncology Reports 40, no. 2 (2018): 1185-1195. https://doi.org/10.3892/or.2018.6500