| Summary: | 碩士 === 國立臺灣大學 === 毒理學研究所 === 96 === Angiogenesis is a process of new blood vessel formation which has essential roles in development, reproduction and repair. In our previous studies, several that the leukocyte cell-derived chemotaxin 2 (LECT2) gene expression was down-regulated with vascular invasion. The levels of LECT2 are clearly correlated with regulating tumor size and overall survival of HCC patients. Using CAM assay, we found that LECT2-transfected cells conditioned media exhibited extremely low angiogenic activity as compared to control cells. This result suggesting that LECT2 may down-regulate certain angiogenic factors. Hence we proposed to investigate the molecular mechanism underlying LECT2 mediated anti-angiogenic factors-induced angiogenesis in vitro and in vivo. Further, we also observed report the expression of LECT2 in others cancer cells.
In this study we evaluated the function of recombinant human LECT2 (rLECT2) proteins on angiogenesis by using human umbilical vein endothelial cells (HUVEC). We demonstrated a selective and significant inhibition of VEGF165 mediated angiogenic activity in HUVEC by rLECT2 protein through inhibiting the VEGF165-induced proliferation, migration and tube formation. The rLECT2 protein also suppressed VEGF165-induced angiogenesis in CAM assay and matrigel plug assay. Both in vitro and in vivo, we found that LECT2 suppressed the VEGF165-induced vascular permeability. Our results demonstrated that rLECT2 protein could reduce the VEGF165-induced VEGFR-2 phosphorylation and inhibited the expression of downstream ERK and AKT phosphorylation in HUVEC. In addition, rLECT2 protein reduced cancer cell conditioned media-induced tube formation in HUVEC and LECT2 also decreased tumor growth of melanoma cells.
In conclusion, we for the first time found that LECT2 played an important role in anti-angiogenesis. Moreover the LECT2 might have broad therapeutic applications in diseases characterized by excessive angiogenesis.
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