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Synthetic murine epidermal growth factor sequence 20-31 is mitogenic and angiogenic
J Nelson1, R Stewart, M McGivern
1School of Biology and Biochemistry, Queen's University of Belfast, UK.
Abstract:
Epidermal growth factor (EGF) and its homologue, transforming growth factor alpha (TGF alpha), are mitogenic, angiogenic and tumour-promoting polypeptides. Much effort has therefore been directed towards the development of EGF/TGF alpha antagonists as a potential cancer therapy. Initial reports that some EGF/TGF alpha synthetic fragments possess EGF-receptor binding activity have not been confirmed in subsequent studies. We have found, however, that the murine EGF B-loop sequence: Ac-[(S-acetamidomethyl)-Cys20,31]-EGF-(20-31)-NH2 [(mEGF-(20-31)] produces biological effects consistent with the parent molecule in bovine, murine, chick and human, but not rat, model systems. In parallel experiments, both mEGF and mEGF-(20-31) elicit migratory, cytoprotective, growth-stimulatory, growth-inhibitory and angiogenic responses. The reverse B-loop sequence, mEGF-(31-20), is also mitogenic and angiogenic. The C-loop sequence, mEGF-(33-42), has no mitogenic or angiogenic activity when applied alone, does not block the mitogenic effect of mEGF, but does block the angiogenic effect of mEGF. It has not been established that the EGF receptor is the target for these fragments, but the results suggest that the residual biological activities of EGF fragments merit further investigation.
Insights
Synthetic fragments of epidermal growth factor (EGF) and transforming growth factor alpha (TGF alpha) show biological activity, including mitogenic and angiogenic effects. These EGF fragments warrant further investigation for potential therapeutic applications.
Area of Science:
- Molecular biology
- Biochemistry
- Cancer research
Background:
- Epidermal growth factor (EGF) and transforming growth factor alpha (TGF alpha) are key polypeptides involved in cell growth, migration, and angiogenesis.
- Their role in tumor promotion has driven research into developing antagonists for cancer therapy.
- Previous attempts to identify EGF/TGF alpha antagonists using synthetic fragments have yielded inconsistent results regarding receptor binding.
Purpose of the Study:
- To investigate the biological activities of synthetic fragments of murine EGF (mEGF).
- To determine if these fragments exhibit effects similar to the parent molecule in various model systems.
- To explore the potential of EGF fragments as therapeutic agents or research tools.
Main Methods:
- Synthesis and characterization of specific EGF fragments, including the B-loop sequence (mEGF-(20-31)) and C-loop sequence (mEGF-(33-42)).
- Testing the biological effects of these fragments in various model systems (bovine, murine, chick, human, and rat).
- Assessing responses such as mitogenesis, angiogenesis, migration, cytoprotection, growth stimulation, and growth inhibition.
Main Results:
- The murine EGF B-loop fragment (mEGF-(20-31)) demonstrated biological effects consistent with the parent mEGF in multiple species, excluding rats.
- Both mEGF and mEGF-(20-31) induced migratory, cytoprotective, growth-stimulatory, growth-inhibitory, and angiogenic responses.
- The reverse B-loop sequence (mEGF-(31-20)) was also found to be mitogenic and angiogenic, while the C-loop sequence (mEGF-(33-42)) inhibited angiogenesis but not mitogenesis.
Conclusions:
- Specific synthetic fragments of EGF, particularly the B-loop sequence, retain significant biological activities, including mitogenic and angiogenic properties.
- These findings suggest that EGF fragments possess inherent biological functions that merit further exploration.
- The study highlights the potential for residual biological activities in EGF fragments, opening avenues for further research in cancer therapy and molecular signaling.