Neutrophils enhance invasion activity of human cholangiocellular carcinoma and hepatocellular carcinoma cells: an in vitro study

J Gastroenterol Hepatol. 2005 Feb;20(2):287-93. doi: 10.1111/j.1440-1746.2004.03575.x.


Background and aim: Tumor-mesenchymal interactions are involved in the mechanism of tumor invasion in several types of carcinoma. Mutual interactions between carcinoma cells and neutrophils, however, have been poorly understood. In the present study we examined the effect of neutrophils on invasion activities of carcinoma cells in vitro. Role of hepatocyte growth factor (HGF) as a mediator was also evaluated.

Methods: Using a Matrigel invasion chamber, invasion activities of HuCC-T1 human cholangiocellular carcinoma cells and HepG2 hepatocellular carcinoma cells in response to recombinant HGF or neutrophils were evaluated.

Results: Recombinant HGF dose-dependently increased invasion activities of HuCC-T1 and HepG2 cells. Neutrophils significantly enhanced invasion activities of these cells, which were suppressed to the respective basal levels with anti-HGF antibody. The carcinoma cells did not secrete HGF. Neutrophils cultivated in tumor condition medium (TCM) of HuCC-T1 or HepG2 cells secreted a significant level of HGF protein without increasing HGF mRNA expression. Treatment with heat or ultrafiltration of TCM of HuCC-T1 or HepG2 cells suggested carcinoma cell-derived HGF inducer(s) to be certain protein(s) with a molecular weight of more than 30 000.

Conclusions: The present study suggests the presence of mutual interactions between HuCC-T1/HepG2 carcinoma cells and neutrophils in tumor invasion via paracrine regulation mediated by neutrophil-derived HGF.

Publication types

  • Comparative Study

MeSH terms

  • Bile Duct Neoplasms / pathology
  • Bile Duct Neoplasms / physiopathology
  • Bile Ducts, Intrahepatic / pathology
  • Blotting, Northern
  • Carcinoma, Hepatocellular / pathology*
  • Carcinoma, Hepatocellular / physiopathology
  • Cholangiocarcinoma / pathology*
  • Cholangiocarcinoma / physiopathology
  • Enzyme-Linked Immunosorbent Assay
  • Hepatocyte Growth Factor / pharmacology
  • Humans
  • In Vitro Techniques
  • Liver Neoplasms / pathology*
  • Liver Neoplasms / physiopathology
  • Neoplasm Invasiveness / pathology
  • Neutrophils / physiology*
  • RNA, Messenger / analysis
  • Tumor Cells, Cultured


  • RNA, Messenger
  • Hepatocyte Growth Factor