TGF-beta3 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 tumour initiation or progression. As recombinant human TGF-beta3 (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 tumour progression. Elevated levels of TGF-beta3 expression detected in late-stage tumours 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-beta3 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-beta1 in tumourigenesis, despite marked differences in biology between the TGF-beta isoforms. Indeed, published studies have indicated that TGF-beta3 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-beta3 is unlikely to influence tumour initiation or progression.