Kupffer cells suppress hepatocarcinogenesis and metastasis in tumor orthotopic implanted Kunming mice

Asian Pac J Cancer Prev. 2013;14(11):6393-8. doi: 10.7314/apjcp.2013.14.11.6393.

Abstract

In this research, we used GdCl3 (gadolinium chloride) to restrain the function of Kupffer cells and assessed effects on hepatocarcinogenesis and metastasis in the Kunming mouse. A 0.25% GdCl3 solution (10 mg/kg b.w.) was infused via the vena caudalis of each mouse 1 week before inoculation of H22 cells and was continued once per three days. Then we observed the follow indexes 3 weeks after injection of H22 cells: tumor weight, histologic characteristics of tumor tissue by light microscopy, ultramicrostructure of Kupffer cells under the electron microscope, distribution and number of Kupffer cells by histochemical staining, and TNF-α and IFN-γ levels in blood-serum and liver tissue by ELISA and RT-PCR. MMP-2 protein expression was tested by immunohistochemistry. The GdCl3 pretreatment had no effect on the quantity of Kupffer cells, but clearly restrained their functions, with decrease of TNF-α and IFN-γ levels and elevation of MMP2. Tumor immunity functions were markedly suppressed and tumor growth was accelerated with appearance of metastasis. Furthermore, survival time of trial mice was shortened.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carcinogenesis / metabolism
  • Carcinogenesis / pathology*
  • Cell Line, Tumor
  • Gadolinium / pharmacology
  • Interferon-gamma / metabolism
  • Kupffer Cells / drug effects
  • Kupffer Cells / metabolism
  • Kupffer Cells / physiology*
  • Liver / drug effects
  • Liver / metabolism
  • Liver / physiopathology*
  • Liver Neoplasms / metabolism
  • Liver Neoplasms / physiopathology*
  • Male
  • Matrix Metalloproteinase 2 / metabolism
  • Mice
  • Neoplasm Metastasis / physiopathology*
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Tumor Necrosis Factor-alpha
  • Interferon-gamma
  • Gadolinium
  • Matrix Metalloproteinase 2
  • gadolinium chloride