Transforming growth factor-beta1 induced hepatocyte apoptosis--a possible mechanism for growth of colorectal liver metastasis

Acta Oncol. 2004;43(1):91-7. doi: 10.1080/02841860310021527.

Abstract

The mechanisms of colonization and growth of metastatic liver tumors from colorectal cancers remain obscure. Forty-three resected colorectal metastatic liver tumors with surrounding livers were evaluated for apoptotic index (AI), proliferation index (PI), and immunohistochemical expressions of TGF-beta1. TGF-beta receptor II, Fas, and Fas-ligand. All the parameters were significantly higher in the peri-tumoral livers than in the tumors with the exception of PI, which was significantly high in tumors. Enhanced TGF-beta1 expression was noticed at the interface between the metastatic tumor and the adjacent liver parenchyma. The AIs of hepatocytes in the TGF-beta1-positive areas (8.7 +/- 7.5%, n = 43) were significantly higher when compared with those in the TGF-beta1-negative areas (2.4 +/- 4.5%, n = 42) (p < 0.001). However, the same kind of correlation could not be found in metastatic tumors. The enhanced expression of TGF-beta1 and hepatocyte apoptosis in the peri-tumoral liver parenchyma may suggest that TGF-beta1 plays a substantial role in the development of colorectal liver metastasis.

Publication types

  • Comparative Study

MeSH terms

  • Aged
  • Apoptosis / physiology
  • Biomarkers, Tumor / analysis*
  • Biopsy, Needle
  • Cells, Cultured
  • Colorectal Neoplasms / pathology*
  • Female
  • Hepatocytes / pathology
  • Hepatocytes / physiology
  • Humans
  • Immunohistochemistry
  • In Situ Nick-End Labeling
  • Ki-67 Antigen / analysis
  • Ki-67 Antigen / metabolism*
  • Liver Neoplasms / pathology
  • Liver Neoplasms / secondary*
  • Male
  • Middle Aged
  • Receptors, Transforming Growth Factor beta / analysis
  • Receptors, Transforming Growth Factor beta / metabolism*
  • Risk Assessment
  • Sensitivity and Specificity
  • fas Receptor / analysis
  • fas Receptor / metabolism*

Substances

  • Biomarkers, Tumor
  • Ki-67 Antigen
  • Receptors, Transforming Growth Factor beta
  • fas Receptor