TGF-β3 and cancer: A review

With the development of growth factors and growth factor modulators as therapeutics for a range of disorders, it is prudent to consider whether modulating the growth factor profile in a tissue can influence turnout initiation or progression. As recombinant human TGF-beta 3 (avotermin) is being developed for the improvement of scarring in the skin it is important to understand the role, if any, of this cytokine in turnout progression. Elevated levels of TGF-beta 3 expression detected in late-stage turnours have linked this cytokine with tumourigenesis, although functional data to support a causative role are lacking. While it has proved tempting for researchers to interpret a 'correlation' as a 'cause' of disease, what has often been overlooked is the normal biological role of TGF-beta 3 in processes that are often subverted in tumourigenesis. Clarifying the role of this cytokine is complicated by inappropriate extrapolation of the data relating to TGF-beta 1 in tumourigenesis, despite marked differences in biology between the TGF-beta isoforms. Indeed, published studies have indicated that TGF-beta 3 may actually play a protective role against tumourigenesis in a range of tissues including the skin, breast, oral and gastric mucosa. Based on currently available data it is reasonable to hypothesize that administration of acute low doses of exogenous TGF-beta 3 is unlikely to influence turnout initiation or progression. (C) 2009 Elsevier Ltd. All rights reserved.