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.