title: Differential expression of protease activity in serum samples of prostate carcinoma patients with metastases.
abstract: We present here the results from MS peptide profiling experiments of prostate carcinoma patients and controls with a specific focus on protease activity-related protein fragments. After purification with surface-active magnetic beads, MALDI-TOF profiling experiments were performed on tryptic digests of serum samples of prostate cancer patients with metastases (n=27) and controls (n=30). This resulted in the reproducible detection of eight differentially expressed peptides, which were then identified by nanoLC-MALDI-TOF/TOF and confirmed by MALDI-FTMS exact mass measurements. All differentially expressed peptides are derived from two homologous parts of human serum albumin; two of the eight peptides were tryptic and six were nontryptic. The presence of the nontryptic fragments indicates that a proteolysis process occurs which is not mediated by trypsin. Since the nontryptic fragments were found at significantly higher levels in control samples compared with metastases samples, it is proposed that a specific proteolytic inhibition process is in effect in the serum of prostate cancer patients. Experiments using synthetic peptides showed that this proteolytic activity occurs ex vivo and is sequence specific. Importantly, the observed prostate carcinoma-related inhibition of the proteolysis was reproduced ex vivo using synthetic peptides.
authors.affiliation: Department of Neurology, Erasmus Medical Center, Rotterdam, The Netherlands.
authors.forename: Lennard J M
authors.initials: LJ
authors.lastname: Dekker
authors.forename: Peter C
authors.initials: PC
authors.lastname: Burgers
authors.forename: Halima
authors.initials: H
authors.lastname: Charif
authors.forename: Angelique L C T
authors.initials: AL
authors.lastname: van Rijswijk
authors.forename: Mark K
authors.initials: MK
authors.lastname: Titulaer
authors.forename: Guido
authors.initials: G
authors.lastname: Jenster
authors.forename: Rainer
authors.initials: R
authors.lastname: Bischoff
authors.forename: Chris H
authors.initials: CH
authors.lastname: Bangma
authors.forename: Theo M
authors.initials: TM
authors.lastname: Luider
mesh_terms: D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D010447:Peptide Hydrolases / Q000097:blood*; D011471:Prostatic Neoplasms / Q000097:blood* / Q000201:enzymology*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D010447:Peptide Hydrolases