Overexpression of CXCR7 induces angiogenic capacity of human hepatocellular carcinoma cells via the AKT signaling pathway

Overexpression of CXCR7 induces angiogenic capacity of human hepatocellular carcinoma cells via the AKT signaling pathway
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DOI:
10.3892/or.2016.5045
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发表时间:
2016-10-01
期刊:
影响因子:
4.2
通讯作者:
Nie, Zhiyu
Nie, Zhiyu
中科院分区:
医学3区
文献类型:
--
作者:
Chen, Yuhui;Teng, Fei;Nie, Zhiyu

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血管生成是肿瘤生长的必要条件,尤其是在肝细胞癌(HCC)中。血管增生与预后差和高侵袭性HCC有关。C-X-C趋化因子受体7型(CXCR7)在许多肿瘤类型中隐含过表达。我们的研究旨在探讨CXCR7在HCC中的功能。采用人脐静脉内皮细胞(HUVECs)成管、Transwell迁移实验和鸡绒毛膜尿囊膜(CAM)实验。我们证实了CXCR7诱导血管生成能力。此外,过表达CXCR7增加了HCC细胞中磷酸化AKT的表达(但不是全部)。此外,过表达CXCR7增加了HCC细胞中肿瘤坏死因子(TNF)- α、白细胞介素(IL)-6和IL-8的表达。此外,LY294002抑制AKT可消除cxcr7诱导的HCC细胞血管生成能力。我们的研究表明,CXCR7通过激活AKT通路在HCC中发挥重要的促血管生成作用。因此,CXCR7可能是HCC抗血管生成治疗的潜在靶点。
Angiogenesis is essential for tumor growth, especially in hepatocellular carcinoma (HCC). The hypervascularity is associated with poor prognosis and highly invasive HCC. The C-X-C chemokine receptor type 7 (CXCR7) has been implied overexpressed in many tumor types. Our study aimed to investigate the CXCR7 function in HCC. The tube formation, Transwell migration assay of human umbilical vein endothelial cells (HUVECs) and chicken chorioallantoic membrane (CAM) assay were used. We confirmed that CXCR7 induces angiogenic capacity. Moreover, overexpressing CXCR7 increased the phosphorylated (but not total) AKT expression in HCC cells. Furthermore, overexpressing CXCR7 increased the expression of tumor necrosis factor (TNF)-alpha, interleukin (IL)-6 and IL-8 in HCC cells. Additionally, inhibition of AKT by LY294002 abrogated CXCR7-induced angiogenic capacity in HCC cells. Our study suggested that CXCR7 plays an important pro-angiogenic role in HCC via activation of the AKT pathway. So CXCR7 may be a potential target for anti-angiogenic therapy in HCC.