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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

A. Mifková, O. Kodet, P. Szabo, J. Kučera, B. Dvořánková, S. André, G. Koripelly, HJ. Gabius, JM. Lehn, K. Smetana,

. 2014 ; 15 (10) : 1465-1470.

Language English Country Germany

Document type Journal Article, Research Support, Non-U.S. Gov't

Grant support
NT13488 MZ0 CEP Register

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.

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