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

被引:129
作者
Albrethsen, J [1 ]
Bogebo, R
Gammeltoft, S
Olsen, J
Winther, B
Raskov, H
机构
[1] Glostrup Cty Hosp, Dept Clin Biochem, DK-2600 Glostrup, Denmark
[2] Glostrup Cty Hosp, Surg Dept D, DK-2600 Glostrup, Denmark
[3] Colotech Ltd, DK-2100 Copenhagen, Denmark
关键词
D O I
10.1186/1471-2407-5-8
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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.
引用
收藏
页数:10
相关论文
共 34 条
[1]   Inflammation and cancer: back to Virchow? [J].
Balkwill, F ;
Mantovani, A .
LANCET, 2001, 357 (9255) :539-545
[2]   THE LEVELS AND BIOLOGIC ACTION OF THE HUMAN NEUTROPHIL GRANULE PEPTIDE HP-1 IN LUNG-TUMORS [J].
BATEMAN, A ;
SINGH, A ;
JOTHY, S ;
FRASER, R ;
ESCH, F ;
SOLOMON, S .
PEPTIDES, 1992, 13 (01) :133-139
[3]  
BATEMAN A, 1991, J BIOL CHEM, V266, P7524
[4]   Identification of defensins in human lymphocyte nuclei [J].
Blomqvist, M ;
Bergquist, J ;
Westman, A ;
Håkansson, K ;
Håkansson, P ;
Fredman, P ;
Ekman, R .
EUROPEAN JOURNAL OF BIOCHEMISTRY, 1999, 263 (02) :312-318
[5]   α-Defensins in the gastrointestinal tract [J].
Cunliffe, RN .
MOLECULAR IMMUNOLOGY, 2003, 40 (07) :463-467
[6]   DIRECT INACTIVATION OF VIRUSES BY HUMAN GRANULOCYTE DEFENSINS [J].
DAHER, KA ;
SELSTED, ME ;
LEHRER, RI .
JOURNAL OF VIROLOGY, 1986, 60 (03) :1068-1074
[7]   Chemokines meet defensins:: the merging concepts of chemoattractants and antimicrobial peptides in host defense [J].
Dürr, M ;
Peschel, A .
INFECTION AND IMMUNITY, 2002, 70 (12) :6515-6517
[8]   Biology and clinical relevance of naturally occurring antimicrobial peptides [J].
Gallo, RL ;
Murakami, M ;
Ohtake, T ;
Zaiou, M .
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, 2002, 110 (06) :823-831
[9]   Versatile defensins [J].
Ganz, T .
SCIENCE, 2002, 298 (5595) :977-+
[10]   Defensins are dominant HLA-DR-associated self-peptides from CD34- peripheral blood mononuclear cells of different tumor patients (plasmacytoma, chronic myeloid leukemia) [J].
Halder, TM ;
Blüggel, M ;
Heinzel, S ;
Pawelec, G ;
Meyer, HE ;
Kalbacher, H .
BLOOD, 2000, 95 (09) :2890-2896