Increased hepcidin expression: A novel oncogenic signalling mechanism

Historically anaemia, which is associated with colorectal cancer, has been attributed to blood loss.

Previous studies have elegantly shown that the anti-microbial peptide hepcidin can also induce anaemia as a consequence of infection and or inflammation. This type of anaemia has been termed anaemia of chronic disease. Thus the primary aim of the recent article by Ward et al published on March 7, 2008 in the World Journal of Gastroenterology was to address whether a component of the anaemia observed in colorectal cancer patients is due to raised hepcidin expression.

Using the technique of mass spectrometry Ward et al clearly demonstrate that whilst circulating hepcidin levels were not associated with anaemia it was positively associated with stage of colorectal disease. Furthermore they show that this peptide which was previously thought to be predominantly expressed by the liver is also expressed in a subset of colorectal cancer tissues.

Dr Chris Tselepis suggests that this study could have ramifications in the diagnosis and treatment of colorectal cancer patients. Furthermore he states that it adds weight to an emerging body of evidence that iron at the level of cancer tissue may amplify carcinogenesis and may explain why early clinical studies using iron chelators have shown great promise.

What this study ultimately suggests is that cancer cells sequester as much iron as is possible so as to feed their high metabolic activity as well as driving cancer pathways. What iron is circulating is likely to be captured by the cellular iron import proteins which are expressed in abundance on the cancer cell surface. In addition, hepcidin expression in cancer cells will inhibit cellular iron export inducing an accumulation of iron thus perpetuating the cancer phenotype.