title: LOXL4 is a selectively expressed candidate diagnostic antigen in head and neck cancer.
abstract: Selective up-regulation of the mRNA of LOXL4, a member of the LOX matrix amine oxidase family, significantly correlated with lymph node metastases and higher tumour stages in head and neck squamous cell carcinomas (HNSCC). To evaluate the diagnostic and prognostic value of the protein we produced an antibody specific for LOXL4 and assessed the expression in 317 human HNSCC specimens. The LOXL4 protein was detected in 92.7% of primary tumours, in 97.8% of lymph node metastases and in affected oral mucosa with high-grade dysplasia, but was absent in various non-neoplastic tissues of the head and neck. TNM categories and overall survival did not link to grades of immunoreactivity. Studies in cultured primary hypopharyngeal HTB-43 carcinoma cells detected perinuclear and cell surface expression of LOXL4, but no nuclear localisation. Therefore, its interactive SRCR-domains and catalytic activity combined with tumour cell specific expression and cell surface associated location indicate multiple functions in tumour cell adhesion and interactions with the extracellular matrix. Our data suggest that LOXL4 is useful both as tumour marker and target in the treatment of HNSCC.
authors.affiliation: Department of Otorhinolaryngology, Head and Neck Surgery, University of Kiel, Arnold-Heller-Strasse 14, Kiel, Germany. jweise@hno.uni-kiel.de
authors.forename: Jan Bernd
authors.initials: JB
authors.lastname: Weise
authors.forename: Pierre
authors.initials: P
authors.lastname: Rudolph
authors.forename: Axel
authors.initials: A
authors.lastname: Heiser
authors.forename: Marie-Luise
authors.initials: ML
authors.lastname: Kruse
authors.forename: Jürgen
authors.initials: J
authors.lastname: Hedderich
authors.forename: Christian
authors.initials: C
authors.lastname: Cordes
authors.forename: Markus
authors.initials: M
authors.lastname: Hoffmann
authors.forename: Ommo
authors.initials: O
authors.lastname: Brant
authors.forename: Petra
authors.initials: P
authors.lastname: Ambrosch
authors.forename: Katalin
authors.initials: K
authors.lastname: Csiszar
authors.forename: Tibor
authors.initials: T
authors.lastname: Görögh
mesh_terms: D000594:Amino Acid Oxidoreductases / Q000378:metabolism*; D000951:Antigens, Neoplasm / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis*; D045744:Cell Line, Tumor; D005260:Female; D005434:Flow Cytometry; D006258:Head and Neck Neoplasms / Q000175:diagnosis*; D006801:Humans; D007150:Immunohistochemistry; D007972:Leukoplakia, Oral / Q000175:diagnosis; D008207:Lymphatic Metastasis; D008297:Male; D018613:Microscopy, Confocal; D008875:Middle Aged; D009061:Mouth Mucosa / Q000378:metabolism; D011230:Precancerous Conditions / Q000175:diagnosis; D008249:Protein-Lysine 6-Oxidase
chemical_list: D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D000594:Amino Acid Oxidoreductases; C445682:LOXL4 protein, human; D008249:Protein-Lysine 6-Oxidase