LOXL4 is a selectively expressed candidate diagnostic antigen in head and neck cancer.
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.
Weise
Jan Bernd
JB
Department of Otorhinolaryngology, Head and Neck Surgery, University of Kiel, Arnold-Heller-Strasse 14, Kiel, Germany. jweise@hno.uni-kiel.de
Rudolph
Pierre
P
Heiser
Axel
A
Kruse
Marie-Luise
ML
Hedderich
Jürgen
J
Cordes
Christian
C
Hoffmann
Markus
M
Brant
Ommo
O
Ambrosch
Petra
P
Csiszar
Katalin
K
Görögh
Tibor
T
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
D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D000594:Amino Acid Oxidoreductases; C445682:LOXL4 protein, human; D008249:Protein-Lysine 6-Oxidase