Open Access
ARTICLE
Heparanase/Syndecan-1 Axis Regulates the Grade of Liver Cancer and Proliferative Ability of Hepatocellular Carcinoma Cells
Shengjin Yu, Huiming Lv, Jinhui Zhang, He Zhang, Weiwei Ju, Yu Jiang*, Lijuan Lin*
Institute of Molecular Medicine, Medical College of Eastern Liaoning University, Dandong, 118003, China
* Corresponding Authors: Yu Jiang. Email: ; Lijuan Lin. Email:
Oncologie 2022, 24(3), 539-551. https://doi.org/10.32604/oncologie.2022.024882
Received 12 June 2022; Accepted 10 August 2022; Issue published 19 September 2022
Abstract
Background: 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.
Materials and Methods: 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.
Results: 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%,
P < 0.05). Heparanase expression was positively correlated with tumor grade, stages, and Ki-
67 expression (
P < 0.05). In contradistinction, both cytoplasmic and membranal syndecan-1 expression exhibited
negative correlations with tumor grade, stages, and Ki-67 expression (
P < 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.
Conclusions: 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.
Keywords
Cite This Article
Yu, S., Lv, H., Zhang, J., Zhang, H., Ju, W. et al. (2022). Heparanase/Syndecan-1 Axis Regulates the Grade of Liver Cancer and Proliferative Ability of Hepatocellular Carcinoma Cells.
Oncologie, 24(3), 539–551.