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SB-431542, an inhibitor of activin receptors, decreases cell growth and migration of mesothelioma cell lines in a dose-dependent way.Activins are members of the transforming growth factor b (TGF-b) superfamily of growth and differentiation factors. Activin A has important physiological roles in cell differentiation, wound healing and inflammation and has the ability to either inhibit or promote growth, depending on the cell type. With respect to cancer, activin A was shown to inhibit cell proliferation in hepatocellular carcinoma, breast cancer or prostate cancer.
In this publication, the authors present activin A as a potential candidate for mesothelioma therapy. They show that activin A is highly expressed in mesothelioma cell lines and in a subset of mesothelioma tissue specimens. Furthermore, they demonstrate that inhibition of activin receptors or silencing of activin A gene expression impairs growth and migration of mesothelioma cells.
No previous reports have been published on the impact of activin A on mesothelioma cell behaviour. The authors also found that recombinant Activin A stimulated clonogenic growth and enhanced cell migration, possibly through the canonical SMAD pathway, similar to the findings described for activin A in oesophageal adenocarcinoma and lung adenocarcinoma. Collectively, these data suggest that in each of these thoracic malignancies activin A has a tumor promoting effect.
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