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.

Reference: Ward DG, Roberts K, Brookes MJ, Joy H, Martin A, Ismail T, Spychal R, Iqbal T, Tselepis C. Increased hepcidin expression in colorectal carcinogenesis. World J Gastroenterol 2008; 14(9): 1339-1345
http://www.wjgnet.com/1007-9327/14/1339.asp

Correspondence to: Dr. Chris Tselepis, CRUK Institute for Cancer Studies, University of Birmingham, Vincent Drive, Birmingham B15 2TH, United Kingdom. c.tselepis@bham.ac.uk
Telephone: +44-121-4142972 Fax: +44-121-6272384

World Journal of Gastroenterology (WJG), a leading international journal in gastroenterology and hepatology, has established a reputation for publishing first class research on esophageal cancer, gastric cancer, liver cancer, viral hepatitis, colorectal cancer, and H pylori infection for providing a forum for both clinicians and scientists. WJG has been indexed and abstracted in Current Contents/Clinical Medicine, Science Citation Index Expanded (also known as SciSearch) and Journal Citation Reports/Science Edition, Index Medicus, MEDLINE and PubMed, Chemical Abstracts, EMBASE/Excerpta Medica, Abstracts Journals, Nature Clinical Practice Gastroenterology and Hepatology, CAB Abstracts and Global Health. ISI JCR 2003-2000 IF: 3.318, 2.532, 1.445 and 0.993. WJG is a weekly journal published by WJG Press. The publication dates are the 7th, 14th, 21st, and 28th day of every month. The WJG is supported by The National Natural Science Foundation of China, No. 30224801 and No. 30424812, and was founded with the name of China National Journal of New Gastroenterology on October 1, 1995, and renamed WJG on January 25, 1998.

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