title: Evaluation of soluble CD44v6 as a potential serum marker for head and neck squamous cell carcinoma.
abstract: In recent years, the measurement of soluble CD44 levels in the circulation of patients with malignant diseases has been introduced as a new and simple diagnostic tool for the detection of human cancer. The high CD44v6 expression in head and neck squamous cell carcinoma (HNSCC) would enable the use of soluble CD44v6 proteins present in the circulation of HNSCC patients as a marker of disease. In the present study, we determined CD44v6 plasma levels using a domain-specific ELISA in healthy volunteers, non-cancer patients, and HNSCC patients before and after surgical removal of the tumor. A difference between the CD44v6 plasma levels of HNSCC patients and controls could not be observed. Moreover, surgical removal of the tumor did not result in a reduction of the CD44v6 plasma level in the HNSCC patients. In addition, the spectrum of soluble v6-containing CD44 proteins present in the plasma of HNSCC patients and controls was determined by immunoprecipitation experiments, but again, tumor-related isoforms could not be distinguished in patient samples. Additional experiments to unravel the biological source of these circulating proteins indicated surprisingly that the v6-containing proteins present in the circulation of healthy individuals are only released in part, if at all, by activated lymphocytes or other nucleated blood cells. Most circulating CD44v6 proteins seem to be derived from the normal epithelial cell compartments, including breast cells, colon cells, and squamous cells. Taken together, these data do not support the use of soluble CD44v6 as a tumor marker in HNSCC or any other tumor type that has developed from tissues producing soluble isoforms.
authors.affiliation: Department of Otolaryngology/Head and Neck Surgery, University Hospital Vrije Universiteit, Amsterdam, The Netherlands.
authors.forename: N L
authors.initials: NL
authors.lastname: Van Hal
authors.forename: G A
authors.initials: GA
authors.lastname: Van Dongen
authors.forename: C B
authors.initials: CB
authors.lastname: Ten Brink
authors.forename: K H
authors.initials: KH
authors.lastname: Heider
authors.forename: I
authors.initials: I
authors.lastname: Rech-Weichselbraun
authors.forename: G B
authors.initials: GB
authors.lastname: Snow
authors.forename: R H
authors.initials: RH
authors.lastname: Brakenhoff
mesh_terms: D000911:Antibodies, Monoclonal; D014408:Biomarkers, Tumor / Q000097:blood*; D001854:Bone Marrow Cells / Q000166:cytology / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000097:blood* / Q000473:pathology / Q000601:surgery; D004797:Enzyme-Linked Immunosorbent Assay; D006023:Glycoproteins / Q000097:blood* / Q000235:genetics; D006258:Head and Neck Neoplasms / Q000097:blood* / Q000473:pathology / Q000601:surgery; D006801:Humans; D018960:Hyaluronan Receptors / Q000097:blood; D007413:Intestinal Mucosa / Q000276:immunology; D008214:Lymphocytes / Q000276:immunology; D009061:Mouth Mucosa / Q000276:immunology; D009367:Neoplasm Staging; D010865:Pilot Projects; D011379:Prognosis; D020033:Protein Isoforms / Q000097:blood / Q000235:genetics; D012016:Reference Values; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012907:Smoking / Q000097:blood / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D014408:Biomarkers, Tumor; C112697:CD44v6 antigen; D006023:Glycoproteins; D018960:Hyaluronan Receptors; D020033:Protein Isoforms