Heparanase overexpression down-regulates syndecan-1 expression in a gallbladder carcinoma cell line

J Int Med Res. 2017 Apr;45(2):662-672. doi: 10.1177/0300060517700323. Epub 2017 Mar 29.

Abstract

Objective To discuss the relevance of heparanase and syndecan-1 and regulation of the heparanase-syndecan1 axis in the invasiveness of gallbladder carcinoma cells. Methods 1. Generation of a gallbladder cancer cell line overexpressing a heparanase (GBD-SD) transgene. 2. Western blot analysis of syndecan-1 levels of GBD-SD and control gallbladder carcinoma (GBC-SD) cells. 3. RT-PCR analysis of syndecan-1 mRNA levels of GBD-SD and GBC-SD. 4. Evaluation of invasion and migration of GBD-SD and GBC-SD cells. Results 1. Heparanase expression in GBD-SD cells was significantly increased. 2. The syndecan-1 mRNA level of GBD-SD cells was significantly lower compared with that of GBC-SD cells. 3. The syndecan-1 DNA copy number in GBD-SD cells was significantly lower compared with that of GBC-SD. 4. The invasiveness and migration of GBD-SD cells were significantly higher compared with GBC-SD cells. Conclusions 1. The expression of heparanase negatively correlated with that of syndecan-1 in a gallbladder carcinoma cell line. 2. The expression of heparanase and syndecan-1 in gallbladder carcinomas negatively correlated, similar to other tumours. 3. The heparanase/syndecan1 axis in gallbladder carcinoma plays an important role in the invasion and metastasis, thus providing a new therapeutic target. 4. Further research is required to identify the detailed mechanisms.

Keywords: Gallbladder carcinoma; RT-PCR; western blot; heparanase; metastasis; syndecan-1.

MeSH terms

  • Cell Line, Tumor
  • Cell Movement
  • DNA Copy Number Variations
  • Epithelial Cells / metabolism
  • Epithelial Cells / pathology
  • Gallbladder / metabolism
  • Gallbladder / pathology
  • Gene Expression
  • Glucuronidase / genetics*
  • Glucuronidase / metabolism
  • Humans
  • Plasmids / chemistry
  • Plasmids / metabolism
  • RNA, Messenger / genetics*
  • RNA, Messenger / metabolism
  • Syndecan-1 / genetics*
  • Syndecan-1 / metabolism
  • Transfection
  • Transgenes

Substances

  • RNA, Messenger
  • Syndecan-1
  • heparanase
  • Glucuronidase