Increased hepcidin expression in colorectal carcinogenesis

被引:87
作者
Ward, Douglas G. [1 ]
Roberts, Keith [1 ]
Brookes, Matthew J. [1 ]
Joy, Howard [1 ]
Martin, Ashley [1 ]
Ismail, Tariq [1 ]
Spychal, Robert [1 ]
Iqbal, Tariq [1 ]
Tselepis, Chris [1 ]
机构
[1] Univ Birmingham, CRUK Inst Canc Studies, Birmingham B15 2TH, W Midlands, England
基金
英国生物技术与生命科学研究理事会;
关键词
iron; hepcidin; colon; cancer; anaemia; mass spectrometry;
D O I
10.3748/wjg.14.1339
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
AIM: 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. CONCLUSION: 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. (c) 2008 WJG. All rights reserved.
引用
收藏
页码:1339 / 1345
页数:7
相关论文
共 30 条
[1]  
Beale AL, 2005, COLORECTAL DIS, V7, P398
[2]  
Becker C, 2005, CELL CYCLE, V4, P217
[3]   Linking colorectal cancer to Wnt signaling [J].
Bienz, M ;
Clevers, H .
CELL, 2000, 103 (02) :311-320
[4]  
BLOEM RM, 1988, NETH J SURG, V40, P121
[5]   A role for iron in Wnt signalling [J].
Brookes, M. J. ;
Boult, J. ;
Roberts, K. ;
Cooper, B. T. ;
Hotchin, N. A. ;
Matthews, G. ;
Iqbal, T. ;
Tselepis, C. .
ONCOGENE, 2008, 27 (07) :966-975
[6]   Modulation of iron transport proteins in human colorectal carcinogenesis [J].
Brookes, M. J. ;
Hughes, S. ;
Turner, F. E. ;
Reynolds, G. ;
Sharma, N. ;
Ismail, T. ;
Berx, G. ;
McKie, A. T. ;
Hotchin, N. ;
Anderson, G. J. ;
Iqbal, T. ;
Tselepis, C. .
GUT, 2006, 55 (10) :1449-1460
[7]   Transferrin receptor 2 is frequently expressed in human cancer cell lines [J].
Calzolari, Alessia ;
Oliviero, Isabella ;
Deaglio, Silvia ;
Mariam, Gualtiero ;
Biffoni, Mauro ;
Sposi, Nadia Maria ;
Malavasi, Fabio ;
Peschle, Cesare ;
Testa, Ugo .
BLOOD CELLS MOLECULES AND DISEASES, 2007, 39 (01) :82-91
[8]   Serum interleukin-6 levels reflect the disease status of colorectal cancer [J].
Chung, YC ;
Chang, YF .
JOURNAL OF SURGICAL ONCOLOGY, 2003, 83 (04) :222-226
[9]   The molecular mechanism of hepcidin-mediated ferroportin down-regulation [J].
De Domenico, Ivana ;
Ward, Diane McVey ;
Langelier, Charles ;
Vaughn, Michael B. ;
Nemeth, Elizabeta ;
Sundquist, Wesley I. ;
Ganz, Tomas ;
Musci, Giovanni ;
Kaplan, Jerry .
MOLECULAR BIOLOGY OF THE CELL, 2007, 18 (07) :2569-2578
[10]   Bone morphogenetic protein-4 is overexpressed in colonic adenocarcinomas and promotes migration and invasion of HCT116 cells [J].
Deng, Haiyun ;
Makizumi, Ryouji ;
Ravikumaya, T. S. ;
Dong, Huali ;
Yang, Wancai ;
Yang, Weng-Lang .
EXPERIMENTAL CELL RESEARCH, 2007, 313 (05) :1033-1044