AXL Overexpression in Tumor-Derived Endothelial Cells Promotes Vessel Metastasis in Patients With Hepatocellular Carcinoma
| Autor: | Shu-Qun Cheng, Hui-Chuan Sun, Xiao-Dong Zhu, Zong-Tao Chai, Jian-Yang Ao, Meng-Chao Wu, Xiu-Ping Zhang, Wan Yee Lau |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Cancer Research vessel metastasis portal vein tumor thrombus Metastasis 03 medical and health sciences 0302 clinical medicine SOX2 Medicine Protein kinase B PI3K/AKT/mTOR pathway RC254-282 Original Research Tube formation business.industry Cell growth Neoplasms. Tumors. Oncology. Including cancer and carcinogens AXL Cell migration hepatocellular carcinoma medicine.disease digestive system diseases endothelial cells 030104 developmental biology Oncology 030220 oncology & carcinogenesis Hepatocellular carcinoma Cancer research business |
| Zdroj: | Frontiers in Oncology Frontiers in Oncology, Vol 11 (2021) |
| ISSN: | 2234-943X |
| DOI: | 10.3389/fonc.2021.650963 |
| Popis: | Portal vein tumor thrombus (PVTT) is one of the most serious forms of hepatocellular carcinoma (HCC) vessel metastasis and has a poor survival rate. However, the molecular mechanism of PVTT has not yet been elucidated. In this study, the molecular mechanism of AXL expressed in tumor-derived endothelial cells (TECs) in vessel metastasis was investigated. High AXL expression was observed in TECs, but not in the tumor cells of HCC patients with PVTT and this was associated with poor overall survival (OS) and disease-free survival (DFS). AXL overexpression was positively associated with CD 31 expression both in vitro and in vivo. AXL promoted the cell proliferation, tube formation, and migration of both TECs and normal endothelial cells (NECs). High expression of AXL in TECs promoted the cell migration, but not the proliferation of HCC cells. Further studies demonstrated that AXL promoted cell migration and tube formation through activation of the PI3K/AKT/SOX2/DKK-1 axis. AXL overexpression in HUVECs promoted tumor growth and liver or vessel metastasis of HCC in xenograft nude mice, which could be counteracted by treatment with R428, an AXL inhibitor. R428 reduced tumor growth and CD 31 expression in HCC in PDX xenograft nude mice. Therefore, AXL over-expression in TECs promotes vessel metastasis of HCC, which indicates that AXL in TECs could be a potential therapeutic target in HCC patients with PVTT. |
| Databáze: | OpenAIRE |
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