Heparanase potentiates the invasion and migration of pancreatic cancer cells via epithelial‑to‑mesenchymal transition through the Wnt/β‑catenin pathway

Oncol Rep. 2020 Aug;44(2):711-721. doi: 10.3892/or.2020.7641. Epub 2020 Jun 10.

Abstract

Mounting evidence indicates that there exists an association between heparanase (HPSE) and several physiological and pathological mechanisms in humans. However, the dynamics of the mechanisms involved in the regulation of HPSE expression in pancreatic cancer (PC) remain unclear. The aim of the present study was to assess the levels of HPSE in PC tissues and cell lines by western blotting and reverse transcription‑quantitative PCR (RT‑qPCR) analysis. Wound healing and Transwell assays were conducted to examine the effects of HPSE on migration and invasion in sh‑NC and sh‑HPSE PC cell lines. In addition, tumor growth was assessed in a mouse xenograft model in vivo. The expression levels of epithelial‑to‑mesenchymal transition (EMT)‑related biomarkers and the involvement of the Wnt/β‑catenin pathway were assessed by analyzing the results of western blot and RT‑qPCR assays. The results indicated that the expression of HPSE was substantially higher in PC tissues and cell lines, whereas experimental knockdown of HPSE suppressed the rates of migration and invasion of PC cells. Western blotting was used to assess the expression of EMT biomarkers and determine the function of HPSE in EMT. Furthermore, our results indicated that downregulation of HPSE expression decreased the expression of Wnt/β‑catenin associated proteins. In conclusion, HPSE appears to be a good candidate as a molecular target for the treatment of PC based on the finding of the present study.

Keywords: pancreatic cancer; heparanase; migration; invasion; epithelial-to-mesenchymal transition.

MeSH terms

  • Aged
  • Animals
  • Biomarkers, Tumor / analysis
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • Cell Line, Tumor
  • Disease-Free Survival
  • Epithelial-Mesenchymal Transition
  • Female
  • Gene Knockdown Techniques
  • Glucuronidase / analysis
  • Glucuronidase / genetics
  • Glucuronidase / metabolism*
  • Humans
  • Male
  • Mice
  • Middle Aged
  • Neoplasm Invasiveness / pathology
  • Neoplasm Staging
  • Pancreas / pathology
  • Pancreas / surgery
  • Pancreatectomy
  • Pancreatic Neoplasms / diagnosis
  • Pancreatic Neoplasms / mortality
  • Pancreatic Neoplasms / pathology*
  • Pancreatic Neoplasms / surgery
  • Prognosis
  • Up-Regulation
  • Wnt Signaling Pathway
  • Xenograft Model Antitumor Assays

Substances

  • Biomarkers, Tumor
  • heparanase
  • Glucuronidase