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BMC Cancer

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Open Access 01-12-2005 | Research article

Upregulated expression of human neutrophil peptides 1, 2 and 3 (HNP 1-3) in colon cancer serum and tumours: a biomarker study

Authors: Jakob Albrethsen, Rikke Bøgebo, Steen Gammeltoft, Jesper Olsen, Benny Winther, Hans Raskov

Published in: BMC Cancer | Issue 1/2005

Abstract

Background

Molecular markers for localized colon tumours and for prognosis following therapy are needed. Proteomics research is currently producing numerous biomarker studies with clinical potential. We investigate the protein composition of plasma and of tumour extracts with the aim of identifying biomarkers for colon cancer.

Methods

By Surface Enhanced Laser Desorption/Ionisation – Time Of Flight / Mass spectrometry (SELDI-TOF/MS) we compare the protein profiles of colon cancer serum with serum from healthy individuals and the protein profiles of colon tumours with normal colon tissue. By size exclusion chromatography, we investigate the binding of HNP 1-3 to high mass plasma proteins. By microflow we investigate the effect of HNP 1-3 on mammalian cells.

Results

Human Neutrophil Peptides -1, -2 and -3 (HNP 1-3), also known as alfa-defensin-1, -2 and -3, are present in elevated concentrations in serum from colon cancer patients and in protein extracts from colon tumours. A fraction of HNP 1-3 in serum is bound to unidentified high mass plasma proteins. HNP 1-3 purified from colon tumours are lethal to mammalian cells.

Conclusions

HNP 1-3 may serve as blood markers for colon cancer in combination with other diagnostic tools. We propose that HNP 1-3 are carried into the bloodstream by attaching to high mass plasma proteins in the tumour microenvironment. We discuss the effect of HNP 1-3 on tumour progression.

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Schoen RE: The case for population-based screening for colorectal cancer. Nat Rev Cancer. 2002, 2 (1): 65-70. 10.1038/nrc705.CrossRefPubMed

Kozak KR, Amneus MW, Pusey SM, Su F, Luong MN, Luong SA, Reddy ST, Farias-Eisner R: Identification of biomarkers for ovarian cancer using strong anion-exchange ProteinChips: potential use in diagnosis and prognosis. Proc Natl Acad Sci U S A. 2003, 100 (21): 12343-12348. 10.1073/pnas.2033602100.CrossRefPubMedPubMedCentral

Melle C, Ernst G, Schimmel B, Bleul A, Koscielny S, Wiesner A, Bogumil R, Moller U, Osterloh D, Halbhuber KJ, Von Eggeling F: Biomarker Discovery and Identification in Laser Microdissected Head and Neck Squamous Cell Carcinoma with ProteinChip(R) Technology, Two-dimensional Gel Electrophoresis, Tandem Mass Spectrometry, and Immunohistochemistry. Mol Cell Proteomics. 2003, 2 (7): 443-452.PubMed

Petricoin EF, Ornstein DK, Paweletz CP, Ardekani A, Hackett PS, Hitt BA, Velassco A, Trucco C, Wiegand L, Wood K, Simone CB, Levine PJ, Linehan WM, Emmert-Buck MR, Steinberg SM, Kohn EC, Liotta LA: Serum proteomic patterns for detection of prostate cancer. J Natl Cancer Inst. 2002, 94 (20): 1576-1578.CrossRefPubMed

Ganz T: Immunology. Versatile defensins. Science. 2002, 298 (5595): 977-979. 10.1126/science.1078708.CrossRefPubMed

Cunliffe RN: Alpha-defensins in the gastrointestinal tract. Mol Immunol. 2003, 40 (7): 463-467. 10.1016/S0161-5890(03)00157-3.CrossRefPubMed

Gallo RL, Murakami M, Ohtake T, Zaiou M: Biology and clinical relevance of naturally occurring antimicrobial peptides. J Allergy Clin Immunol. 2002, 110 (6): 823-831. 10.1067/mai.2002.129801.CrossRefPubMed

Ihi T, Nakazato M, Mukae H, Matsukura S: Elevated concentrations of human neutrophil peptides in plasma, blood, and body fluids from patients with infections. Clin Infect Dis. 1997, 25 (5): 1134-1140.CrossRefPubMed

Panyutich AV, Panyutich EA, Krapivin VA, Baturevich EA, Ganz T: Plasma defensin concentrations are elevated in patients with septicemia or bacterial meningitis. J Lab Clin Med. 1993, 122 (2): 202-207.PubMed

10.

Vlahou A, Schellhammer PF, Mendrinos S, Patel K, Kondylis FI, Gong L, Nasim S, Wright Jr GLJ: Development of a novel proteomic approach for the detection of transitional cell carcinoma of the bladder in urine. Am J Pathol. 2001, 158 (4): 1491-1502.CrossRefPubMedPubMedCentral

11.

Mizukawa N, Sugiyama K, Fukunaga J, Ueno T, Mishima K, Takagi S, Sugahara T: Defensin-1, a peptide detected in the saliva of oral squamous cell carcinoma patients. Anticancer Res. 1998, 18 (6B): 4645-4649.PubMed

12.

Zhou L, Huang LQ, Beuerman RW, Grigg ME, Li SF, Chew FT, Ang L, Stern ME, Tan D: Proteomic analysis of human tears: defensin expression after ocular surface surgery. J Proteome Res. 2004, 3 (3): 410-416. 10.1021/pr034065n.CrossRefPubMed

13.

Bateman A, Singh A, Jothy S, Fraser R, Esch F, Solomon S: The levels and biologic action of the human neutrophil granule peptide HP-1 in lung tumors. Peptides. 1992, 13 (1): 133-139. 10.1016/0196-9781(92)90152-S.CrossRefPubMed

14.

Mizukawa N, Sugiyama K, Kamio M, Yamachika E, Ueno T, Fukunaga J, Takagi S, Sugahara T: Immunohistochemical staining of human alpha-defensin-1 (HNP-1), in the submandibular glands of patients with oral carcinomas. Anticancer Res. 2000, 20 (2B): 1125-1127.PubMed

15.

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. Am J Pathol. 2002, 160 (4): 1311-1324.CrossRefPubMedPubMedCentral

16.

Bateman A, Singh A, Shustik C, Mars WM, Solomon S: The isolation and identification of multiple forms of the neutrophil granule peptides from human leukemic cells. J Biol Chem. 1991, 266 (12): 7524-7530.PubMed

17.

Schluesener H, Meyermann R: Neutrophilic defensins penetrate the blood-brain barrier. J Neurosci Res. 1995, 42 (5): 718-723. 10.1002/jnr.490420515.CrossRefPubMed

18.

Lundy FT, Orr DF, Gallagher JR, Maxwell P, Shaw C, Napier SS, Gerald Cowan C, 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 Oncol. 2004, 40 (2): 139-144. 10.1016/S1368-8375(03)00142-8.CrossRefPubMed

19.

Van Wetering S, Mannesse-Lazeroms SP, Van Sterkenburg MA, Daha MR, Dijkman JH, Hiemstra PS: Effect of defensins on interleukin-8 synthesis in airway epithelial cells. Am J Physiol. 1997, 272 (5 Pt 1): L888-96.PubMed

20.

Kagan BL, Selsted ME, Ganz T, Lehrer RI: Antimicrobial defensin peptides form voltage-dependent ion-permeable channels in planar lipid bilayer membranes. Proc Natl Acad Sci U S A. 1990, 87 (1): 210-214.CrossRefPubMedPubMedCentral

21.

Hill CP, Yee J, Selsted ME, Eisenberg D: Crystal structure of defensin HNP-3, an amphiphilic dimer: mechanisms of membrane permeabilization. Science. 1991, 251 (5000): 1481-1485.CrossRefPubMed

22.

Panyutich A, Ganz T: Activated alpha 2-macroglobulin is a principal defensin-binding protein. Am J Respir Cell Mol Biol. 1991, 5 (2): 101-106.CrossRefPubMed

23.

Panyutich AV, Szold O, Poon PH, Tseng Y, Ganz T: Identification of defensin binding to C1 complement. FEBS Lett. 1994, 356 (2-3): 169-173. 10.1016/0014-5793(94)01261-X.CrossRefPubMed

24.

Daher KA, Selsted ME, Lehrer RI: Direct inactivation of viruses by human granulocyte defensins. J Virol. 1986, 60 (3): 1068-1074.PubMedPubMedCentral

25.

Lichtenstein A, Ganz T, Selsted ME, Lehrer RI: In vitro tumor cell cytolysis mediated by peptide defensins of human and rabbit granulocytes. Blood. 1986, 68 (6): 1407-1410.PubMed

26.

Yang D, Chertov O, Bykovskaia SN, Chen Q, Buffo MJ, Shogan J, Anderson M, Schroder JM, Wang JM, Howard OM, Oppenheim JJ: Beta-defensins: linking innate and adaptive immunity through dendritic and T cell CCR6. Science. 1999, 286 (5439): 525-528. 10.1126/science.286.5439.525.CrossRefPubMed

27.

Durr M, Peschel A: Chemokines meet defensins: the merging concepts of chemoattractants and antimicrobial peptides in host defense. Infect Immun. 2002, 70 (12): 6515-6517. 10.1128/IAI.70.12.6515-6517.2002.CrossRefPubMedPubMedCentral

28.

Blomqvist M, Bergquist J, Westman A, Hakansson K, Hakansson P, Fredman P, Ekman R: Identification of defensins in human lymphocyte nuclei. Eur J Biochem. 1999, 263 (2): 312-318. 10.1046/j.1432-1327.1999.00495.x.CrossRefPubMed

29.

Misuno NI, Kolesnikova TS, Lerer RI, Gants T, Voitenok NN: [Effects of human defensin HNP-1 on the production of tumor necrosis factor-alpha by human blood monocytes in vitro]. Biull Eksp Biol Med. 1992, 113 (5): 524-527.PubMed

30.

Halder TM, Bluggel M, Heinzel S, Pawelec G, Meyer HE, Kalbacher H: Defensins are dominant HLA-DR-associated self-peptides from CD34(-) peripheral blood mononuclear cells of different tumor patients (plasmacytoma, chronic myeloid leukemia). Blood. 2000, 95 (9): 2890-2896.PubMed

31.

Yang D, Biragyn A, Kwak LW, Oppenheim JJ: Mammalian defensins in immunity: more than just microbicidal. Trends Immunol. 2002, 23 (6): 291-296. 10.1016/S1471-4906(02)02246-9.CrossRefPubMed

32.

Welling MM, Hiemstra PS, van den Barselaar MT, Paulusma-Annema A, Nibbering PH, Pauwels EK, Calame W: Antibacterial activity of human neutrophil defensins in experimental infections in mice is accompanied by increased leukocyte accumulation. J Clin Invest. 1998, 102 (8): 1583-1590.CrossRefPubMedPubMedCentral

33.

Balkwill F, Mantovani A: Inflammation and cancer: back to Virchow?. Lancet. 2001, 357 (9255): 539-545. 10.1016/S0140-6736(00)04046-0.CrossRefPubMed

34.

van Kempen LC, Ruiter DJ, van Muijen GN, Coussens LM: The tumor microenvironment: a critical determinant of neoplastic evolution. Eur J Cell Biol. 2003, 82 (11): 539-548.CrossRefPubMed

The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2407/5/8/prepub

Title: Upregulated expression of human neutrophil peptides 1, 2 and 3 (HNP 1-3) in colon cancer serum and tumours: a biomarker study
Authors: Jakob Albrethsen
Rikke Bøgebo
Steen Gammeltoft
Jesper Olsen
Benny Winther
Hans Raskov
Publication date: 01-12-2005
Publisher: BioMed Central
Published in: BMC Cancer / Issue 1/2005
Electronic ISSN: 1471-2407
DOI: https://doi.org/10.1186/1471-2407-5-8

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Abstract

Background

Methods

Results

Conclusions

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