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

• Published in: Chembiochem : a European journal of chemical biology 2014-07, Vol.15 (10), p.1465-1470
• Main Authors: Mifková, Alžběta, Kodet, Ondřej, Szabo, Pavol, Kučera, Jan, Dvořánková, Barbora, André, Sabine, Koripelly, Girish, Gabius, Hans-Joachim, Lehn, Jean-Marie, Smetana Jr, Karel
• Format: Article
• Language: English
• Subjects: actin; Actins - metabolism; Animals; cancer; Cells, Cultured; Dermis - cytology; Dermis - drug effects; Fibroblasts - drug effects; Fibroblasts - pathology; galectin; Galectin 1 - metabolism; Humans; Myofibroblasts - drug effects; Myofibroblasts - pathology; Neoplasms - drug therapy; Neoplasms - metabolism; Neoplasms - pathology; Polyamines - chemistry; Polyamines - pharmacology; polycations; Rats; tenascin; Transforming Growth Factor beta1 - metabolism; Tumor Cells, Cultured
• ISSN: 1439-4227; 1439-7633
• DOI: 10.1002/cbic.201402087

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. Don't start! (But do go on) TGF‐β1 stimulates the conversion of fibroblasts to smooth muscle α‐actin (SMA)‐positive myofibroblasts. The polyamine BPA‐C8 inhibits this conversion, but has no effect on cells that already express SMA. It also reduces the occurrence of an extracellular matrix around the activated fibroblasts. BPA‐C8 could thus interfere with fibroblasts' effect on tumor progression.