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 type7(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.
Highlights
Angiogenesis, the creation of new blood vessels, is an important effector of many physiological and pathological processes [1]
Many of anti‐angiogenesis drugs serve as inhibiting pro‐angiogenic factors, such as the monoclonal antibody bevacizumab binds to vascular endothelial growth factor (VEGF), or other small molecules that inhibit the binding of VEGF [15,16]
The qRT‐PCR showed that C‐X‐C chemokine receptor type 7 (CXCR7) mRNA level was obviously increased in HCCLM3 compared to the SMMC‐7721 (Fig. 1A)
Summary
Angiogenesis, the creation of new blood vessels, is an important effector of many physiological and pathological processes [1]. Angiogenesis occurs to induce tumor growth and metastasis, and represents a key hallmark of tumor development [2,3,4,5]. Tumor angiogenesis provides the nutrients and oxygen to maintain tumor growth and invasion. Inhibition of tumor angiogenesis may decrease tumor cell growth The mechanisms of tumor angiogenesis are not yet entirely understood and specific, effective inhibitors of angiogenesis are required for cancer therapy
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