Increased hepcidin expression in colorectal carcinogenesis.
OBJECTIVE
To investigate whether the iron stores regulator hepcidin is implicated in colon cancer-associated anaemia and whether it might have a role in colorectal carcinogenesis.


METHODS
Mass spectrometry (MALDI-TOF MS and SELDI-TOF MS) was employed to measure hepcidin in urine collected from 56 patients with colorectal cancer. Quantitative Real Time RT-PCR was utilised to determine hepcidin mRNA expression in colorectal cancer tissue. Hepcidin cellular localisation was determined using immunohistochemistry.


RESULTS
We demonstrate that whilst urinary hepcidin expression was not correlated with anaemia it was positively associated with increasing T-stage of colorectal cancer (P<0.05). Furthermore, we report that hepcidin mRNA is expressed in 34% of colorectal cancer tissue specimens and was correlated with ferroportin repression. This was supported by hepcidin immunoreactivity in colorectal cancer tissue.


CONCLUSIONS
We demonstrate that systemic hepcidin expression is unlikely to be the cause of the systemic anaemia associated with colorectal cancer. However, we demonstrate for the first time that hepcidin is expressed by colorectal cancer tissue and that this may represent a novel oncogenic signalling mechanism.
Ward
Douglas G
DG
CRUK Institute for Cancer Studies, University of Birmingham, Vincent Drive, Birmingham B15 2TH, United Kingdom.
Roberts
Keith
K
Brookes
Matthew J
MJ
Joy
Howard
H
Martin
Ashley
A
Ismail
Tariq
T
Spychal
Robert
R
Iqbal
Tariq
T
Tselepis
Chris
C
D000740:Anemia / Q000209:etiology / Q000378:metabolism*; D023181:Antimicrobial Cationic Peptides / Q000235:genetics / Q000378:metabolism* / Q000652:urine; D014408:Biomarkers, Tumor / Q000652:urine; D015179:Colorectal Neoplasms / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D064451:Hepcidins; D006801:Humans; D009367:Neoplasm Staging; D012333:RNA, Messenger / Q000378:metabolism; D015203:Reproducibility of Results; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
D023181:Antimicrobial Cationic Peptides; D014408:Biomarkers, Tumor; C578702:HAMP protein, human; D064451:Hepcidins; D012333:RNA, Messenger