CXCR7 silencing inhibits the migration and invasion of human tumor endothelial cells derived from hepatocellular carcinoma by suppressing STAT3

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 phosphory-lation 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.