A37
Is there a role for hepcidin in human cancers?
Douglas Ward, Samuel Ford, John Carrigan, Ulrich Gunther, Tariq Iqbal, Philip Johnson, Chris Tselpis
University of Birmingham, UK
Background
Iron excess is detrimental to health and is associated with carcinogenesis. This association is unsurprising since iron is prerequisite for driving cellular proliferation and ATP generation. We have previously shown that cancer cells have a selective advantage in over expressing proteins involved in iron acquisition and by repressing the function of cellular iron efflux. This ultimately allows cells to capture and withhold iron which in turn can drive several oncogenic signalling pathways. The prime candidate for suppressing iron efflux is the peptide hormone hepcidin, however, what the exact role of hepcidin in carcinogenesis to date has not been studied.
Method
Utilising a mass spectrometry based hepcidin assay we have analysed serum hepcidin levels in patients with a range of common cancers including colorectal cancer. We have also examined hepcidin transcript levels in tumour and adjacent non-tumour tissue using qRT-PCR. In addition we have assessed the in vitro effect of hepcidin on cell phenotype and both the cellular proteome and metabolome.
Results
Serum levels of hepcidin were not substantially altered in cancer patients, but hepcidin mRNA was elevated in approximately 30% of colorectal cancer specimens examined compared to normal colonic tissue. Addition of hepcidin to a number of cancer cells lines including the oesophageal adenocarcinoma cell line OE33 was associated with increased cellular proliferation and viability which was coupled with alterations in both the proteome and metabolome.
Conclusion
Whilst systemic levels of hepcidin might not influence tumourigenesis it is likely that hepcidin synthesis within the tumour itself may cause the block of cellular iron efflux which serves to elevate the cellular iron level. This increased intracellular iron level inevitably modulates multiple signalling pathways which culminate in changes in the metabolome and proteome.
