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Updated: Jun 21, 2026
Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells
Published on: October 27, 2020
TGF-beta3 and cancer: a review
H G Laverty1, L M Wakefield, N L Occleston
1Renovo Group Plc, Core Technology Facility, 48 Grafton Street, Manchester M13 9XX, UK.
Abstract:
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.
Insights
Transforming growth factor-beta3 (TGF-beta3) may protect against cancer. Current data suggest that low doses of TGF-beta3 are unlikely to impact tumor development, despite some studies linking it to tumor progression.
Area of Science:
- Oncology
- Cell Biology
- Wound Healing
Background:
- Growth factors are emerging as therapeutics, prompting investigation into their role in tumorigenesis.
- Recombinant human TGF-beta3 (avotermin) is being developed for scar improvement, necessitating an understanding of its role in tumor progression.
- Elevated TGF-beta3 in late-stage tumors suggests a link to cancer, but functional data are lacking.
Purpose of the Study:
- To clarify the role of TGF-beta3 in tumor initiation and progression.
- To differentiate the function of TGF-beta3 from other TGF-beta isoforms (e.g., TGF-beta1) in cancer.
- To evaluate the potential impact of exogenous TGF-beta3 administration on tumorigenesis.
Main Methods:
- Review of existing literature on TGF-beta3 expression and function in various cancers.
- Analysis of studies investigating the normal biological roles of TGF-beta3.
- Comparison of TGF-beta3 data with data from other TGF-beta isoforms.
Main Results:
- Published studies suggest TGF-beta3 may have a protective role against tumorigenesis in skin, breast, and mucosal tissues.
- The normal biological functions of TGF-beta3 may be subverted during cancer development.
- Extrapolation of data from TGF-beta1 to TGF-beta3 is inappropriate due to distinct biological activities.
Conclusions:
- TGF-beta3's role in tumorigenesis is complex and potentially protective, contrary to some correlational findings.
- Acute, low-dose administration of exogenous TGF-beta3 is unlikely to influence tumor initiation or progression.
- Further research is needed to fully elucidate the dual role of TGF-beta3 in cancer biology.
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