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CXCR7的过表达通过AKT信号通路诱导人肝癌细胞的血管生成能力。

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

作者信息

Chen Yuhui, Teng Fei, Wang Geying, Nie Zhiyu

机构信息

Department of Neurology, Shanghai Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, P.R. China.

出版信息

Oncol Rep. 2016 Oct;36(4):2275-81. doi: 10.3892/or.2016.5045. Epub 2016 Aug 25.

Abstract

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)‑α, 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.

摘要

血管生成对于肿瘤生长至关重要,尤其是在肝细胞癌(HCC)中。血管过度增生与预后不良及高侵袭性的HCC相关。C-X-C趋化因子受体7型(CXCR7)在许多肿瘤类型中均有过表达。我们的研究旨在探究CXCR7在HCC中的功能。采用了人脐静脉内皮细胞(HUVECs)的管腔形成实验、Transwell迁移实验以及鸡胚绒毛尿囊膜(CAM)实验。我们证实CXCR7可诱导血管生成能力。此外,过表达CXCR7可增加HCC细胞中磷酸化(而非总)AKT的表达。再者,过表达CXCR7可增加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。另外,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途径在HCC中发挥重要的促血管生成作用。因此,CXCR7可能是HCC抗血管生成治疗的一个潜在靶点。

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