Active TGF-beta1 correlates with myofibroblasts and malignancy in the colorectal adenoma-carcinoma sequence

Cancer Sci. 2009 Apr;100(4):663-70. doi: 10.1111/j.1349-7006.2009.01100.x.


Transforming growth factor-beta1 (TGF-beta1), a cytokine involved in various stages of cancer, is produced as a latent complex and requires processing to become active. We have determined total and active TGF-beta1 levels in homogenates of colorectal neoplasia. In contrast to total TGF-b levels, showing a stepwise increase in the mucosa-adenoma-carcinoma sequence, active TGF-beta1 levels are increased only in carcinomas but not in premalignant adenomas. Furthermore, solely active TGF-beta1 levels are associated with the stage of the carcinomas and worse patient prognosis. Active TGF-beta1 levels correlated significantly with plasminogen activator inhibitor (PAI)-1, alpha-smooth muscle actin (SMA) and several matrix-remodeling proteinases. Interestingly, SMA levels are also significantly increased in colorectal carcinomas but not in adenomas, suggesting that despite the enhanced total TGF-beta1 levels, myofibroblast accumulation is not (yet) occurring in these premalignant neoplasias. The correlation between active TGF-beta1 and SMA expression in tumors indicates that tumor-promoting myofibroblasts might arise as a result of increased TGF-beta1 activation. These data underline the significance of the interaction between malignant cells and (myo)-fibroblasts in the tumor microenvironment, modulating the biologic behavior of colorectal cancer.

MeSH terms

  • Actins / metabolism
  • Adenoma / metabolism*
  • Adenoma / pathology
  • Biomarkers, Tumor / metabolism
  • Carcinoma / metabolism*
  • Carcinoma / pathology
  • Colorectal Neoplasms / metabolism*
  • Colorectal Neoplasms / pathology
  • Desmin / metabolism
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Fibroblasts / metabolism*
  • Fibroblasts / pathology
  • HT29 Cells
  • Humans
  • Immunohistochemistry
  • Keratins / metabolism
  • Male
  • Muscle, Smooth / metabolism*
  • Muscle, Smooth / pathology
  • Plasminogen Activator Inhibitor 1 / metabolism
  • Reproducibility of Results
  • Sensitivity and Specificity
  • Smad2 Protein / metabolism
  • Transforming Growth Factor beta1 / metabolism*
  • Urokinase-Type Plasminogen Activator / metabolism
  • Vimentin / metabolism


  • Actins
  • Biomarkers, Tumor
  • Desmin
  • Plasminogen Activator Inhibitor 1
  • SMAD2 protein, human
  • Smad2 Protein
  • Transforming Growth Factor beta1
  • Vimentin
  • Keratins
  • Urokinase-Type Plasminogen Activator