Upregulated expression of human neutrophil peptides 1, 2 and 3 (HNP 1-3) in colon cancer serum and tumours: a biomarker study.
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.
Albrethsen
Jakob
J
Department of Clinical Biochemistry, Glostrup Hospital, 2600 Glostrup, Denmark. ja@dcb-glostrup.dk
Bøgebo
Rikke
R
Gammeltoft
Steen
S
Olsen
Jesper
J
Winther
Benny
B
Raskov
Hans
H
D000818:Animals; D014408:Biomarkers, Tumor / Q000097:blood* / Q000302:isolation & purification / Q000378:metabolism; D002460:Cell Line; D002850:Chromatography, Gel; D003110:Colonic Neoplasms / Q000097:blood / Q000175:diagnosis* / Q000378:metabolism; D004285:Dogs; D006801:Humans; D018675:Toxicity Tests; D015854:Up-Regulation; D023084:alpha-Defensins / Q000097:blood* / Q000302:isolation & purification / Q000378:metabolism
D014408:Biomarkers, Tumor; D023084:alpha-Defensins; C406413:human neutrophil peptide 1; C406416:human neutrophil peptide 2; C406427:human neutrophil peptide 3