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Published in: BMC Cancer 1/2010

Open Access 01-12-2010 | Research article

Defensin alpha 6 (DEFA 6) overexpression threshold of over 60 fold can distinguish between adenoma and fully blown colon carcinoma in individual patients

Authors: Mariya Y Radeva, Franziska Jahns, Anne Wilhelm, Michael Glei, Utz Settmacher, Karl Otto Greulich, Henning Mothes

Published in: BMC Cancer | Issue 1/2010

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Abstract

Background

It is known that alpha-defensin expression is enhanced in colon cancer. However, the expression of human alpha defensin 6 (DEFA 6) in earlier stages, such as adenoma, has so far not yet been studied in a patient resolved manner.

Methods

By using quantitative Real Time-PCR, the gene expression pattern of DEFA 1-3 and DEFA 6 was analyzed in tissue of different stages of carcinogenesis, derived from colorectal cancer patients. In addition to paired normal and tumor tissue, matched normal near tumor and adenoma tissue samples were examined.

Results

The median gene expression of human defensin alpha 6 (DEFA 6) has been found to be moderately increased (~ 5 fold) in tumor samples derived from individuals with colorectal cancer (CRC) when compared to their normal counterparts. However, when the data were analyzed in a patient-wise manner, a large expression variation among individual patients is found, making the use of DEFA 6 for individual diagnosis of fully blown colon carcinoma difficult. Surprisingly, in adenoma the gene expression analysis revealed a 100 fold increased median expression of DEFA 6 relative to normal colon tissue. 13/18 samples had an individual overexpression of more than 60 fold in adenoma but only 3/17 in carcinoma. In each of the individual patients, at least either the adenoma or the carcinoma showed strong DEFA 6 overexpression.

Conclusions

We suggest that the expression of DEFA 6 preferably can be used as a potential diagnostic marker for adenoma and not as a marker for fully blown carcinoma. This is supported by the fact that DEFA 6 is a downstream target of the Wnt pathway, which is mutational active during the earliest stage of cancer development.
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Literature
1.
go back to reference Menendez A, Finlay BB: Defensins in the immunology of bacterial infections. Current Opinion in Immunology. 2007, 19: 385-391. 10.1016/j.coi.2007.06.008.CrossRefPubMed Menendez A, Finlay BB: Defensins in the immunology of bacterial infections. Current Opinion in Immunology. 2007, 19: 385-391. 10.1016/j.coi.2007.06.008.CrossRefPubMed
2.
go back to reference Kuwano K, Tanaka N, Shimizu T, Kida Y: Antimicrobial activity of inducible human beta defensin-2 against Mycoplasma pneumoniae. Current Microbiology. 2006, 52: 435-438. 10.1007/s00284-005-0215-7.CrossRefPubMed Kuwano K, Tanaka N, Shimizu T, Kida Y: Antimicrobial activity of inducible human beta defensin-2 against Mycoplasma pneumoniae. Current Microbiology. 2006, 52: 435-438. 10.1007/s00284-005-0215-7.CrossRefPubMed
3.
go back to reference Cunliffe RN, Kamal M, Rose FRAJ, James PD, Mahida YR: Expression of antimicrobial neutrophil defensins in epithelial cells of active inflammatory bowel disease mucosa. Journal of Clinical Pathology. 2002, 55: 298-304.CrossRefPubMedPubMedCentral Cunliffe RN, Kamal M, Rose FRAJ, James PD, Mahida YR: Expression of antimicrobial neutrophil defensins in epithelial cells of active inflammatory bowel disease mucosa. Journal of Clinical Pathology. 2002, 55: 298-304.CrossRefPubMedPubMedCentral
4.
go back to reference Hill CP, Yee J, Selsted ME, Eisenberg D: Crystal structure of defensin HNP-3, an amphiphilic dimer: mechanisms of membrane permeabilization. Science. 1991, 251: 1481-1485. 10.1126/science.2006422.CrossRefPubMed Hill CP, Yee J, Selsted ME, Eisenberg D: Crystal structure of defensin HNP-3, an amphiphilic dimer: mechanisms of membrane permeabilization. Science. 1991, 251: 1481-1485. 10.1126/science.2006422.CrossRefPubMed
5.
go back to reference Cunliffe RN, Mahida YR: Expression and regulation of antimicrobial peptides in the gastrointestinal tract. J Leukoc Biol. 2004, 75: 49-58. 10.1189/jlb.0503249.CrossRefPubMed Cunliffe RN, Mahida YR: Expression and regulation of antimicrobial peptides in the gastrointestinal tract. J Leukoc Biol. 2004, 75: 49-58. 10.1189/jlb.0503249.CrossRefPubMed
6.
go back to reference Melle C, Ernst G, Schimmel B, Bleul A, Thieme H, Kaufmann R, Mothes H, Settmacher U, Claussen U, Halbhuber KJ, von Eggeling F: Discovery and identification of alpha-defensins as low abundant, tumor-derived serum markers in colorectal cancer. Gastroenterology. 2005, 129: 66-73. 10.1053/j.gastro.2005.05.014.CrossRefPubMed Melle C, Ernst G, Schimmel B, Bleul A, Thieme H, Kaufmann R, Mothes H, Settmacher U, Claussen U, Halbhuber KJ, von Eggeling F: Discovery and identification of alpha-defensins as low abundant, tumor-derived serum markers in colorectal cancer. Gastroenterology. 2005, 129: 66-73. 10.1053/j.gastro.2005.05.014.CrossRefPubMed
7.
go back to reference Muller CA, Markovic-Lipkovski J, Klatt T, Gamper J, Schwarz G, Beck H, Deeg M, Kalbacher H, Widmann S, Wessels JT, Becker V, Muller GA, Flad T: Human alpha-defensins HNPs-1,-2, and-3 in renal cell carcinoma - Influences on tumor cell proliferation. American Journal of Pathology. 2002, 160: 1311-1324.CrossRefPubMedPubMedCentral Muller CA, Markovic-Lipkovski J, Klatt T, Gamper J, Schwarz G, Beck H, Deeg M, Kalbacher H, Widmann S, Wessels JT, Becker V, Muller GA, Flad T: Human alpha-defensins HNPs-1,-2, and-3 in renal cell carcinoma - Influences on tumor cell proliferation. American Journal of Pathology. 2002, 160: 1311-1324.CrossRefPubMedPubMedCentral
8.
go back to reference Holterman DA, Diaz JI, Blackmore PF, Davis JW, Schellhammer PF, Corica A, Semmes OJ, Vlahou A: Overexpression of alpha-defensin is associated with bladder cancer invasiveness. Urol Oncol. 2006, 24: 97-108.CrossRefPubMed Holterman DA, Diaz JI, Blackmore PF, Davis JW, Schellhammer PF, Corica A, Semmes OJ, Vlahou A: Overexpression of alpha-defensin is associated with bladder cancer invasiveness. Urol Oncol. 2006, 24: 97-108.CrossRefPubMed
9.
go back to reference Lundy FT, Orr DF, Gallagher JR, Maxwell P, Shaw C, Napier SS, Cowan CG, Lamey PJ, Marley JJ: Identification and overexpression of human neutrophil alpha-defensins (human neutrophil peptides 1, 2 and 3) in squamous cell carcinomas of the human tongue. Oral Oncology. 2004, 40: 139-144. 10.1016/S1368-8375(03)00142-8.CrossRefPubMed Lundy FT, Orr DF, Gallagher JR, Maxwell P, Shaw C, Napier SS, Cowan CG, Lamey PJ, Marley JJ: Identification and overexpression of human neutrophil alpha-defensins (human neutrophil peptides 1, 2 and 3) in squamous cell carcinomas of the human tongue. Oral Oncology. 2004, 40: 139-144. 10.1016/S1368-8375(03)00142-8.CrossRefPubMed
10.
go back to reference Albrethsen J, Bogebo R, Gammeltoft S, Olsen J, Winther B, Raskov H: Upregulated expression of human neutrophil peptides 1, 2 and 3 (HNP 1-3) in colon cancer serum and tumours: a biomarker study. Bmc Cancer. 2005, 5: 10.1186/1471-2407-5-8. Albrethsen J, Bogebo R, Gammeltoft S, Olsen J, Winther B, Raskov H: Upregulated expression of human neutrophil peptides 1, 2 and 3 (HNP 1-3) in colon cancer serum and tumours: a biomarker study. Bmc Cancer. 2005, 5: 10.1186/1471-2407-5-8.
11.
go back to reference Nam MJ, Kee MK, Kuick R, Hanash SM: Identification of defensin alpha 6 as a potential biomarker in colon adenocarcinoma. Journal of Biological Chemistry. 2005, 280: 8260-8265. 10.1074/jbc.M410054200.CrossRefPubMed Nam MJ, Kee MK, Kuick R, Hanash SM: Identification of defensin alpha 6 as a potential biomarker in colon adenocarcinoma. Journal of Biological Chemistry. 2005, 280: 8260-8265. 10.1074/jbc.M410054200.CrossRefPubMed
12.
go back to reference Albrethsen J, Moller CH, Olsen J, Raskov H, Gammeltoft S: Human neutrophil peptides 1, 2 and 3 are biochemical markers for metastatic colorectal cancer. European Journal of Cancer. 2006, 42: 3057-3064. 10.1016/j.ejca.2006.05.039.CrossRefPubMed Albrethsen J, Moller CH, Olsen J, Raskov H, Gammeltoft S: Human neutrophil peptides 1, 2 and 3 are biochemical markers for metastatic colorectal cancer. European Journal of Cancer. 2006, 42: 3057-3064. 10.1016/j.ejca.2006.05.039.CrossRefPubMed
13.
go back to reference Radeva M, Hofmann T, Altenberg B, Mothes H, Richter KK, Pool-Zobel B, Greulich KO: The database dbEST correctly predicts gene expression in colon cancer patients. Curr Pharm Biotechnol. 2008, 9: 510-515. 10.2174/138920108786786330.CrossRefPubMed Radeva M, Hofmann T, Altenberg B, Mothes H, Richter KK, Pool-Zobel B, Greulich KO: The database dbEST correctly predicts gene expression in colon cancer patients. Curr Pharm Biotechnol. 2008, 9: 510-515. 10.2174/138920108786786330.CrossRefPubMed
14.
go back to reference Daher KA, Lehrer RI, Ganz T, Kronenberg M: Isolation and Characterization of Human Defensin Cdna Clones. Proceedings of the National Academy of Sciences of the United States of America. 1988, 85: 7327-7331. 10.1073/pnas.85.19.7327.CrossRefPubMedPubMedCentral Daher KA, Lehrer RI, Ganz T, Kronenberg M: Isolation and Characterization of Human Defensin Cdna Clones. Proceedings of the National Academy of Sciences of the United States of America. 1988, 85: 7327-7331. 10.1073/pnas.85.19.7327.CrossRefPubMedPubMedCentral
15.
go back to reference Zhang K, Lu QH, Zhang Q, Hu X: Regulation of activities of NK cells and CD4 expression in T cells by human HNP-1,-2, and-3. Biochemical and Biophysical Research Communications. 2004, 323: 437-444. 10.1016/j.bbrc.2004.08.111.CrossRefPubMed Zhang K, Lu QH, Zhang Q, Hu X: Regulation of activities of NK cells and CD4 expression in T cells by human HNP-1,-2, and-3. Biochemical and Biophysical Research Communications. 2004, 323: 437-444. 10.1016/j.bbrc.2004.08.111.CrossRefPubMed
16.
go back to reference Zou H, Harrington JJ, Sugumar A, Klatt KK, Smyrk TC, Ahlquist DA: Detection of colorectal disease by stool defensin assay: An exploratory study. Clinical Gastroenterology and Hepatology. 2007, 5: 865-868. 10.1016/j.cgh.2007.03.013.CrossRefPubMed Zou H, Harrington JJ, Sugumar A, Klatt KK, Smyrk TC, Ahlquist DA: Detection of colorectal disease by stool defensin assay: An exploratory study. Clinical Gastroenterology and Hepatology. 2007, 5: 865-868. 10.1016/j.cgh.2007.03.013.CrossRefPubMed
17.
go back to reference Hiyama T, Yokozaki H, Kitadai Y, Tahara E, Tahara H, Ide T, Haruma K, Yasui W, Kajiyama G, Tahara E: In situ mRNA hybridization technique for analysis of human telomerase RNA in gastric precancerous and cancerous lesions. Jpn J Cancer Res. 1998, 89: 1187-1194.CrossRefPubMed Hiyama T, Yokozaki H, Kitadai Y, Tahara E, Tahara H, Ide T, Haruma K, Yasui W, Kajiyama G, Tahara E: In situ mRNA hybridization technique for analysis of human telomerase RNA in gastric precancerous and cancerous lesions. Jpn J Cancer Res. 1998, 89: 1187-1194.CrossRefPubMed
18.
go back to reference Arango D, Mariadason JM, Wilson AJ, Yang W, Corner GA, Nicholas C, Aranes MJ, Augenlicht LH: c-Myc overexpression sensitises colon cancer cells to camptothecin-induced apoptosis. Br J Cancer. 2003, 89: 1757-1765. 10.1038/sj.bjc.6601338.CrossRefPubMedPubMedCentral Arango D, Mariadason JM, Wilson AJ, Yang W, Corner GA, Nicholas C, Aranes MJ, Augenlicht LH: c-Myc overexpression sensitises colon cancer cells to camptothecin-induced apoptosis. Br J Cancer. 2003, 89: 1757-1765. 10.1038/sj.bjc.6601338.CrossRefPubMedPubMedCentral
19.
go back to reference Andreu P, Colnot S, Godard C, Gad S, Chafey P, Niwa-Kawakita M, Laurent-Puig P, Kahn A, Robine S, Perret C, Romagnolo B: Crypt-restricted proliferation and commitment to the Paneth cell lineage following Apc loss in the mouse intestine. Development. 2005, 132: 1443-1451. 10.1242/dev.01700.CrossRefPubMed Andreu P, Colnot S, Godard C, Gad S, Chafey P, Niwa-Kawakita M, Laurent-Puig P, Kahn A, Robine S, Perret C, Romagnolo B: Crypt-restricted proliferation and commitment to the Paneth cell lineage following Apc loss in the mouse intestine. Development. 2005, 132: 1443-1451. 10.1242/dev.01700.CrossRefPubMed
Metadata
Title
Defensin alpha 6 (DEFA 6) overexpression threshold of over 60 fold can distinguish between adenoma and fully blown colon carcinoma in individual patients
Authors
Mariya Y Radeva
Franziska Jahns
Anne Wilhelm
Michael Glei
Utz Settmacher
Karl Otto Greulich
Henning Mothes
Publication date
01-12-2010
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2010
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/1471-2407-10-588

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