@Article{oncologie.2022.024882,
AUTHOR = {Shengjin Yu, Huiming Lv, Jinhui Zhang, He Zhang, Weiwei Ju, Yu Jiang, Lijuan Lin},
TITLE = {Heparanase/Syndecan-1 Axis Regulates the Grade of Liver Cancer and Proliferative Ability of Hepatocellular Carcinoma Cells},
JOURNAL = {Oncologie},
VOLUME = {24},
YEAR = {2022},
NUMBER = {3},
PAGES = {539--551},
URL = {http://www.techscience.com/oncologie/v24n3/49724},
ISSN = {1765-2839},
ABSTRACT = {<b>Background:</b> Although heparanase/syndecan-1 axis is involved in malignant progression of many cancers, its
significance in liver cancer is not well understood. In this study, we explored the value of heparanase/syndecan-1 axis
expression in liver cancer and the intervention mechanisms that target this axis by inhibiting the proliferation of
hepatocellular carcinoma cells. <b>Materials and Methods:</b> We conducted tissue microarray analysis that included
90 primary liver cancer and their corresponding adjacent samples to evaluate the expression of heparanase and syndecan-1 and their correlation with clinicopathologic characteristics. RNA interference and western blot assays were
performed to analyze the effect of heparanase on syndecan-1 expression in human hepatocellular carcinoma cells
MHCC97-H. Cell proliferative capability, Erk and Akt signaling molecules were respectively detected with CCK-
8, cell colony formation and western blot assays after the treatment of low molecular weight heparin (LMWH)
and syndecan-1 monoclonal antibody. <b>Results:</b> Heparanase showed a high positive rates (75.56%) in liver cancer
patients. The cellular positivity for membrane-located syndecan-1 was less in liver cancer (36.67%) compared with
adjacent tissue (57.78%, <i>P</i> < 0.05). Heparanase expression was positively correlated with tumor grade, stages, and Ki-
67 expression (<i>P</i> < 0.05). In contradistinction, both cytoplasmic and membranal syndecan-1 expression exhibited
negative correlations with tumor grade, stages, and Ki-67 expression (<i>P</i> < 0.05). Transfection with a heparanase
small-interfering RNA resulted in a significant rise in membrane syndecan-1 expression but a marked decline in
shed syndecan-1. LMWH and syndecan-1 monoclonal antibody notably inhibited cellular proliferation. Further studies revealed that LMWH and syndecan-1 monoclonal antibody significantly down-regulated Erk and Akt phosphorylation. <b>Conclusions:</b> Heparanase and syndecan-1 present a contrary correlation with the malignant
capability of liver cancer, but work together to facilitate the proliferation of hepatocellular carcinoma cells that
can be attenuated by LMWH and syndecan-1 monoclonal antibody by inhibiting Erk and Akt signals.},
DOI = {10.32604/oncologie.2022.024882}
}