Heparanase-1-induced shedding of heparan sulfate from syndecan-1 in hepatocarcinoma cell facilitates lymphatic endothelial cell proliferation via VEGF-C/ERK pathway

作者：Yu, Shengjin; Lv, Huiming; Zhang, He; Jiang, Yu; Hong, Yu; Xia, Rongjun; Zhang, Qifang; Ju, Weiwei; Jiang, Lili; Ou, Geng; Zhang, Jinhui; Wang, Shujing^*; Zhang, Jianing

来源：Biochemical and Biophysical Research Communications, 2017, 485(2): 432-439.

DOI：10.1016/j.bbrc.2017.02.060

• Heparanase-1
• Syndecan-1
• Heparan sulfate
• VEGF-C

Heparanase-1/syndecan-1 axis plays critical roles in tumorigenesis and development. The main mechanism includes heparanase-1 (HPA-1) degrades the heparan sulfate chain of syndecan-1 (SDC-1), and the following shedding of heparan sulfate from tumor cell releases and activates SDC-1 sequestered growth factors. However, the significance of Heparanase-1/syndecan-1 axis and its effects on the microenvironment of lymphatic metastasis in hepatocellular carcinogenesis (HCC) procession have not been reported. Herein, we found that IPA-1 could degrade the heparan sulfate on hepatocarcinoma cell surface. Importantly, HPA-1-induced shedding of heparan sulfate chain from SDC-1 facilitated the release of vascular endothelial growth factor C (VEGF-C) from SDC-1/VEGF-C complex into the medium of hepatocarcinoma cell. Further studies indicated that VEGF-C secretion from hepatocarcinoma cell promoted lymphatic endothelial cell growth through activating extracellular signal-regulated kinase (ERIC) signaling. Taken together, this study reveals a novel existence of Heparanase-1/syndecan-1 axis in hepatocarcinoma cell and its roles in the cross-talking with the microenvironment of lymphatic metastasis.

• 出版日期2017-4-1
• 单位大连医科大学; 大连理工大学; 中国医科大学; 辽东学院