Synthetic polyamine BPA-C8 inhibits TGF-β1-mediated conversion of human dermal fibroblast to myofibroblasts and establishment of galectin-1-rich extracellular matrix in vitro

Chembiochem. 2014 Jul 7;15(10):1465-70. doi: 10.1002/cbic.201402087. Epub 2014 May 27.

Abstract

Cancer-associated fibroblasts (CAFs) play a role in the progression of malignant tumors. They are formed by conversion of fibroblasts to smooth muscle α-actin-positive (SMA-positive) myofibroblasts. Polyamines are known to change the arrangement of the actin cytoskeleton by binding to the anionic actin. We tested the effect of the synthetic polyamine BPA-C8 on the transition of human dermal fibroblasts to myofibroblasts induced either by TGF-β1 alone or by TGF-β1 together with adhesion/growth-regulatory galectin-1. Pre-existing CAFs, myofibroblasts from pancreatitis, and rat smooth muscle cells were also exposed to BPA-C8. BPA-C8 impaired myofibroblast formation from activated fibroblasts, but it had no effect on cells already expressing SMA. BPA-C8 also reduced the occurrence of an extracellular matrix around the activated fibroblasts. The reported data thus extend current insights into polyamine activity, adding interference with tumor progression to the tumor-promoting processes warranting study.

Keywords: actin; cancer; galectin; polycations; tenascin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / metabolism
  • Animals
  • Cells, Cultured
  • Dermis / cytology
  • Dermis / drug effects
  • Fibroblasts / drug effects
  • Fibroblasts / pathology*
  • Galectin 1 / metabolism*
  • Humans
  • Myofibroblasts / drug effects*
  • Myofibroblasts / pathology*
  • Neoplasms / drug therapy
  • Neoplasms / metabolism
  • Neoplasms / pathology
  • Polyamines / chemistry*
  • Polyamines / pharmacology*
  • Rats
  • Transforming Growth Factor beta1 / metabolism*
  • Tumor Cells, Cultured

Substances

  • Actins
  • Galectin 1
  • Polyamines
  • Transforming Growth Factor beta1