Abstract
C-X-C chemokine receptor type 7 (CXCR7) is reported to be overexpressed in tumor endothelial cells (TECs), which are the primary target cells of antivascular chemotherapy. However, the role of CXCR7 in TECs is not fully understood. In the present study, CXCR7 expression was inhibited in TECs derived from hepatocellular carcinoma (HCC) using short hairpin (sh)RNA plasmids to investigate the role of CXCR7 in the regulation of migration and invasion of TECs as well as its underlying mechanisms. The data showed that the downregulation of CXCR7 significantly inhibited the migration and invasion of TECs. Further study showed that silencing CXCR7 resulted in decreased phosphorylated signal transducer and activator of transcription 3 (STAT3) at Tyr705 and its downstream target genes in TECs, including matrix metalloproteinase‑2 (MMP2) and vascular endothelial growth factor (VEGF). However, restoring STAT3 phosphorylation abolished the CXCR7‑shRNA‑induced decrease in TECs migration and invasion, as well as the downregulation of MMP2 and VEGF in TECs. These findings indicate that CXCR7 may regulate the migration and invasion of TECs derived from HCC via the STAT3 signaling pathway and that CXCR7 could be a potential target for the antivascular therapy of HCC.
Highlights
Hepatocellular carcinoma (HCC) is one of the most common and lethal malignancies worldwide, especially in Asia and Africa [1]
In the current study, we investigated the effect of C‐X‐C chemokine receptor type 7 (CXCR7) silencing on the migration and invasion of tumor endothelial cells (TECs) derived from HCC in vitro and further explored the mechanisms involved in CXCR7‐regulated migration and invasion of TECs derived from HCC
WU et al: INHIBITION OF CXCR7 ON TECs demonstrate that CXCR7 is an important molecule in regulating the migration and invasion of TECs derived from HCC by triggering the signal transducer and activator of transcription 3 (STAT3) pathway
Summary
Hepatocellular carcinoma (HCC) is one of the most common and lethal malignancies worldwide, especially in Asia and Africa [1]. The main cause of cancer‐related deaths in HCC patients is tumor metastasis, which relies on angiogenesis [2]. It has been proposed that the metastatic activity of tumors is related to whether they have acquired an angiogenic phenotype (the ability to recruit vasculature), which enables them to obtain adequate nutrition and oxygen by angiogenesis [3,4]. The migratory and invasive capacities of TECs enable them to degrade the surrounding ECM and migrate towards pro‐angiogenic cues to form neovessels. Understanding the mechanisms that regulate the migration and invasion of TECs is very important for the antiangiogenic therapy of cancer
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