Inhibition of VEGF 165/VEGFR2-dependent signaling by LECT2 suppresses hepatocellular carcinoma angiogenesis

Chi Kuan Chen, Wen Hsuan Yu, Tsu Yao Cheng, Min Wei Chen, Chia Yi Su, Yi Chieh Yang, Tsang Chih Kuo, Ming Tsan Lin, Ya Chi Huang, Michael Hsiao, Kuo Tai Hua*, Mien Chie Hung, Min Liang Kuo

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

29 Scopus citations

Abstract

Hepatocellular carcinoma (HCC) relies on angiogenesis for growth and metastasis. Leukocyte cell-derived chemotaxin 2 (LECT2) is a cytokine and preferentially expressed in the liver. Previous studies have found that LECT2 targets to both immune and tumor cells to suppress HCC development and vascular invasion. Although LECT2 did not affect HCC cells growth in vitro, it still suppressed HCC xenografts growth in immune-deficient mice, suggesting other cells such as stroma cells may also be targeted by LECT2. Here, we sought to determine the role of LECT2 in tumor angiogenesis in HCC patients. We found that LECT2 expression inhibited tumor growth via angiogenesis in the HCC xenograft model. Specifically, we demonstrated that recombinant human LECT2 protein selectively suppressed vascular endothelial growth factor (VEGF) 165-induced endothelial cell proliferation, migration, and tube formation in vitro and in vivo. Mechanistically, LECT2 reduced VEGF receptor 2 tyrosine phosphorylation and its downstream extracellular signal-regulated kinase and AKT phosphorylation. Furthermore, LECT2 gene expression correlated negatively with angiogenesis in HCC patients. Taken together, our findings demonstrate that LECT2 inhibits VEGF 165-induced HCC angiogenesis through directly binding to VEGFR2 and has broad applications in treating VEGF-mediated solid tumors.

Original languageEnglish
Article number31398
JournalScientific reports
Volume6
DOIs
StatePublished - 10 Aug 2016

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