title: Plasma levels of OLFM4 in normals and patients with gastrointestinal cancer.
abstract: Olfactomedin 4 (OLFM4) is a secreted glycoprotein predominantly expressed in bone marrow and gastrointestinal tissues. Aberrant expression of OLFM4 has been shown in several cancers. However, the clinical significance hereof is currently controversial. OLFM4 has been proposed as a candidate biomarker of gastrointestinal cancers. To address this, we developed monoclonal antibodies against synthetic peptides representing various segments of OLFM4. We examined expression of OLFM4 in epithelial cells by immunohistochemistry and found that OLFM4 is highly expressed in proliferating benign epithelial cells and in some carcinoma cells. We developed an Enzyme Linked Immunosorbent Assay for OLFM4 and investigated whether plasma levels of OLFM4 reflect colorectal malignancies, but were unable to see any such association. Instead, we observed two populations of individuals with respect to OLFM4 levels in plasma, the majority with OLFM4 in plasma between 0 and 0.1 μg/ml, mean 0.028 μg/ml while 10% of both normals and patients with cancers had OLFM4 between 4 and 60 μg/ml, mean 15 μg/ml. The levels were constant over time. The background for this high plasma level is not known, but must be taken into account if OLFM4 is used as biomarker for GI cancers.
authors.affiliation: The Granulocyte Research Laboratory, Department of Hematology, National University Hospital, Copenhagen, Denmark.
authors.forename: Stine N
authors.initials: SN
authors.lastname: Clemmensen
authors.affiliation: Department of Pathology, National University Hospital, Copenhagen, Denmark.
authors.forename: Anders J
authors.initials: AJ
authors.lastname: Glenthøj
authors.affiliation: Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Sara
authors.initials: S
authors.lastname: Heebøll
authors.affiliation: Department of Surgical Gastroenterology, Hvidovre Hospital, Hvidovre, Denmark.
authors.forename: Hans Jørgen
authors.initials: HJ
authors.lastname: Nielsen
authors.affiliation: Department of Biomedicine, University of Southern Denmark, Odense, Denmark.
authors.forename: Claus
authors.initials: C
authors.lastname: Koch
authors.affiliation: The Granulocyte Research Laboratory, Department of Hematology, National University Hospital, Copenhagen, Denmark.
authors.forename: Niels
authors.initials: N
authors.lastname: Borregaard
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015153:Blotting, Western; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D004847:Epithelial Cells / Q000378:metabolism*; D005234:Fatty Liver / Q000235:genetics; D005260:Female; D005770:Gastrointestinal Neoplasms / Q000097:blood* / Q000235:genetics / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D016179:Granulocyte Colony-Stimulating Factor / Q000097:blood* / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis
chemical_list: C454127:OLFM4 protein, human; D016179:Granulocyte Colony-Stimulating Factor
keywords: colorectal cancer; intestinal stem cells; monoclonal antibodies; neutrophil subsets; olfactomedin 4