Overexpression of sulfatase-1 in murine hepatocarcinoma Hca-F cell line downregulates mesothelin and leads to reduction in lymphatic metastasis, both in vitro and in vivo

Oncotarget. 2016 Nov 15;7(46):75052-75063. doi: 10.18632/oncotarget.11933.

Abstract

Lymphatic vessels function as transport channels for tumor cells to metastasize from the primary site into the lymph nodes. In this experiment we evaluated the effect of Sulfatase-1 (Sulf-1) on metastasis by upregulating it in murine hepatocarcinoma cell line Hca-F with high lymph node metastatic rate of >75%. The study in vitro showed that up regulation of Sulf-1 in Hca-F cells significantly reduced cell proliferation, migration and invasion (p<0.05). Also, the forced expression of Sulf-1 down regulated Mesothelin (Msln) at both the protein and mRNA levels. The experiment in vivo further showed that up-regulation of Sulf-1 with the attendant downregulation of mesothelin delayed tumor growth and decreased lymph node metastasis. In conclusion, our findings show that Sulf-1 is an important tumor suppressor gene in hepatocellular carcinoma (HCC), and its over expression downregulates Msln and results in a decrease in HCC cell proliferation, migration, invasion, and lymphatic metastasis. This functional relationship between Sulf-1 and Msln could be exploited for the development of a novel liver cancer therapy.

Keywords: hepatocellular carcinoma; lymph node metastasis; mesothelin; migration and invasion; sulfatase-1.

MeSH terms

  • Animals
  • Carcinoma, Hepatocellular / genetics*
  • Carcinoma, Hepatocellular / pathology*
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Cell Transformation, Neoplastic / genetics
  • Cell Transformation, Neoplastic / metabolism
  • Down-Regulation
  • GPI-Linked Proteins / genetics*
  • GPI-Linked Proteins / metabolism
  • Gene Expression Regulation, Neoplastic*
  • Liver Neoplasms / genetics*
  • Liver Neoplasms / pathology*
  • Lymph Nodes / pathology
  • Lymphatic Metastasis
  • Mesothelin
  • Mice
  • Sulfotransferases / genetics*
  • Sulfotransferases / metabolism

Substances

  • GPI-Linked Proteins
  • Msln protein, mouse
  • Sulf1 protein, mouse
  • Sulfotransferases
  • Mesothelin