Speaker
Alesia Ivashkevich
(Centre for Innate Immunity and Infectious Disease, Monash Institute of Medical Research, Monash University, 27-31 Wright Street, Clayton, Victoria, 3168, Australia)
Description
Late normal tissue side effects from cancer radiotherapy can manifest as fibrosis and severely affect quality of life. Decreasing the treatment dose to spare the normal tissues and avoid fibrosis interferes with the efficiency of tumour control. Discovery of novel treatments to avoid adverse responses to radiation would benefit radiotherapy outcomes immensely. Exon expression analysis performed in primary fibroblasts derived from cancer patients who developed fibrosis or not, has revealed that activin and its inhibitor, follistatin, are induced by IR. Activin A is a member of the TGFβ cytokine superfamily and is a potent regulator of the inflammatory response and tissue fibrosis. Follistatin binds activin A with high affinity and results in its inactivation. We have also measured intracellular and secreted follistatin in IR-treated fibroblasts over time and found that protein levels correlated well with the detected IR-induced follistatin and activin A mRNA levels.
Furthermore, comparison between fibrosis patients and control samples revealed lower levels of follistatin transcripts in patients who developed severe fibrosis. Hence, the data indicate a potential role for follistatin in the radiation response and ultimately fibrosis mitigation. Further characterization of the cellular signalling and transcriptional targets of follistatin and associated factors will provide novel biological insights into the molecular pathology of fibrosis and establish potential therapeutical targets for fibrosis prevention and treatment.
Primary author
Alesia Ivashkevich
(Centre for Innate Immunity and Infectious Disease, Monash Institute of Medical Research, Monash University, 27-31 Wright Street, Clayton, Victoria, 3168, Australia)
