Synthetic Polyamine BPA-C8 Inhibits TGF-beta 1-Mediated Conversion of Human Dermal Fibroblast to Myofibroblasts and Establishment of Galectin-1-Rich Extracellular Matrix in Vitro
Abstract
Cancer-associated fibroblasts (CAFs) play a role in the progression of malignant tumors. They are formed by conversion of fibroblasts to smooth muscle alpha-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-beta 1 alone or by TGF-beta 1 together with adhesion/growth-regulatory galectin-1.
Pre-existing CAFs, myofi-broblasts 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.