title: Heparanase-1-induced shedding of heparan sulfate from syndecan-1 in hepatocarcinoma cell facilitates lymphatic endothelial cell proliferation via VEGF-C/ERK pathway.
abstract: 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 HPA-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 (ERK) 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.
authors.affiliation: Institute of Molecular Medicine, Medical College of Eastern Liaoning University, Dandong 118000, Liaoning, China.
authors.forename: Shengjin
authors.initials: S
authors.lastname: Yu
authors.affiliation: Institute of Molecular Medicine, Medical College of Eastern Liaoning University, Dandong 118000, Liaoning, China.
authors.forename: Huiming
authors.initials: H
authors.lastname: Lv
authors.affiliation: Institute of Molecular Medicine, Medical College of Eastern Liaoning University, Dandong 118000, Liaoning, China.
authors.forename: He
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Institute of Molecular Medicine, Medical College of Eastern Liaoning University, Dandong 118000, Liaoning, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: Institute of Molecular Medicine, Medical College of Eastern Liaoning University, Dandong 118000, Liaoning, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Hong
authors.affiliation: Institute of Molecular Medicine, Medical College of Eastern Liaoning University, Dandong 118000, Liaoning, China.
authors.forename: Rongjun
authors.initials: R
authors.lastname: Xia
authors.affiliation: Institute of Molecular Medicine, Medical College of Eastern Liaoning University, Dandong 118000, Liaoning, China.
authors.forename: Qifang
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Institute of Molecular Medicine, Medical College of Eastern Liaoning University, Dandong 118000, Liaoning, China.
authors.forename: Weiwei
authors.initials: W
authors.lastname: Ju
authors.affiliation: Institute of Molecular Medicine, Medical College of Eastern Liaoning University, Dandong 118000, Liaoning, China.
authors.forename: Lili
authors.initials: L
authors.lastname: Jiang
authors.affiliation: First Affiliated Hospital of China Medical University, Shenyang 110000, Liaoning, China.
authors.forename: Geng
authors.initials: G
authors.lastname: Ou
authors.affiliation: Institute of Molecular Medicine, Medical College of Eastern Liaoning University, Dandong 118000, Liaoning, China. Electronic address: yxyzjh@163.com.
authors.forename: Jinhui
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Institute of Glycobiology, Dalian Medical University, Dalian 116044, Liaoning, China. Electronic address: wangshujing@dlmedu.edu.cn.
authors.forename: Shujing
authors.initials: S
authors.lastname: Wang
authors.affiliation: School of Life Science and Medicine, Dalian University of Technology, Panjin 124221, Liaoning, China. Electronic address: jnzhang@dlut.edu.cn.
authors.forename: Jianing
authors.initials: J
authors.lastname: Zhang
mesh_terms: D000818:Animals; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D042783:Endothelial Cells / Q000378:metabolism*; D005966:Glucuronidase / Q000235:genetics / Q000378:metabolism*; D006497:Heparan Sulfate / Q000378:metabolism*; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008207:Lymphatic Metastasis; D042601:Lymphatic Vessels / Q000166:cytology; D020935:MAP Kinase Signaling System; D051379:Mice; D011485:Protein Binding; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D053668:Syndecan-1 / Q000235:genetics / Q000378:metabolism*; D059016:Tumor Microenvironment; D042582:Vascular Endothelial Growth Factor C / Q000378:metabolism*; D000099175:Heparanase
chemical_list: D005966:Glucuronidase; D006497:Heparan Sulfate; D053668:Syndecan-1; D042582:Vascular Endothelial Growth Factor C; D000099175:Heparanase
keywords: Heparan sulfate; Heparanase-1; Syndecan-1; VEGF-C