The potential role of brain-derived neurotrophic factor (BDNF) in angiogenesis

Abstract

Background and Aim: Hepatocellular carcinoma (HCC) is a hypervascularized solid tumor, where angiogenesis plays an essential role. The molecular mechanism of angiogenesis remains largely unclear. The present study aims to investigate the potential role of BDNF, one member of the neurotrophin family, in the angiogenic behavior of endothelial cells. Materials and methods: One normal mouse endothelial cell line (MILE SVEN 1) and one tumor-derived endothelial cell line (SVEC4-10EE2) were used in an in vitro setting. These two cell lines were treated with recombinant BDNF protein, TrkB blocker-K252a and BDNF combined with K252a. The viability of cells was determined by MTT assay, and VEGF were detected by semiquantitative a The expression of BDNF, HIF-1 RTPCR and Western blot. Results: The two cell lines expressed different levels of endogenous BDNF. The tumor-derived endothelial cells, which had a higher level of endogenous BDNF, demonstrated a higher proliferation rate than the normal endothelial cells, which had a lower endogenous BDNF level. Exogenous BDNF administration could promote cell proliferation in both cell lines. The tumor-derived endothelial cell line expressed BDNF receptor p75NTR, whereas the normal endothelial cell line expressed another BDNF receptor TrkB. BDNF and VEGF in the tumor-derived a upregulated the expression of BDNF, HIF-1 endothelial cells, but it could only augment the expression of BDNF and VEGF in the normal endothelial cells. Conclusion: BDNF might play an important role in mediating the angiogenic behavior of endothelial cells in both pathological and physiological conditions through different molecular pathways.