title: Overexpression of TACE and TIMP3 mRNA in head and neck cancer: association with tumour development and progression.
abstract: BACKGROUND
  TACE/ADAM17 is a transmembranous protease that cleaves membrane-bound growth factors like EGFR ligands. TACE-dependent proteolysis is regulated by its inhibitor, tissue inhibitor of metalloproteinases 3 (TIMP3). This study analyses the role of TACE and TIMP3 mRNA expression in squamous cell carcinomas of the head and neck (HNSCCs).
  
  
  METHODS
  We analysed TACE and TIMP3 mRNA expression in HNSCCs from 106 patients by RNA in situ hybridisation.
  
  
  RESULTS
  TACE mRNA was upregulated in HNSCCs compared with dysplastic (P<0.05) and normal epithelia (P<0.001), with strong hybridisation signals in 21.9% of invasive tumour tissues and 4.5% of dysplasia. Elevated mRNA levels were accompanied by increased amounts of TACE protein in HNSCCs. TIMP3 mRNA expression in HNSCC-associated stroma was significantly higher than in the stroma adjacent to dysplastic or normal epithelia. Expression of TACE mRNA in HNSCCs was associated with tumour stage (P=0.019) and regional lymph node metastasis (P=0.009). Furthermore, levels of TACE mRNA in HNSCCs correlated with the expression of TIMP3 mRNA in HNSCC-associated stroma. Concomitantly, patients expressing high levels of TACE and TIMP3 mRNA showed significantly reduced overall survival compared with those with low mRNA levels.
  
  
  CONCLUSIONS
  Our results indicate an important role of TACE and TIMP3 during development and progression of HNSCCs.
authors.affiliation: Institute of Tumor Biology, Center of Experimental Medicine, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany.
authors.forename: J-W
authors.initials: JW
authors.lastname: Kornfeld
authors.forename: S
authors.initials: S
authors.lastname: Meder
authors.forename: M
authors.initials: M
authors.lastname: Wohlberg
authors.forename: R E
authors.initials: RE
authors.lastname: Friedrich
authors.forename: T
authors.initials: T
authors.lastname: Rau
authors.forename: L
authors.initials: L
authors.lastname: Riethdorf
authors.forename: T
authors.initials: T
authors.lastname: Löning
authors.forename: K
authors.initials: K
authors.lastname: Pantel
authors.forename: S
authors.initials: S
authors.lastname: Riethdorf
mesh_terms: D051722:ADAM Proteins / Q000235:genetics* / Q000378:metabolism; D000072198:ADAM17 Protein; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D002277:Carcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002294:Carcinoma, Squamous Cell; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006258:Head and Neck Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D007124:Immunoenzyme Techniques; D017403:In Situ Hybridization; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D018307:Neoplasms, Squamous Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D011379:Prognosis; D015347:RNA Probes; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D000077195:Squamous Cell Carcinoma of Head and Neck; D015996:Survival Rate; D019717:Tissue Inhibitor of Metalloproteinase-3 / Q000235:genetics* / Q000378:metabolism; D014407:Tumor Cells, Cultured
chemical_list: D014408:Biomarkers, Tumor; D015347:RNA Probes; D012333:RNA, Messenger; C088390:TIMP3 protein, human; D019717:Tissue Inhibitor of Metalloproteinase-3; D051722:ADAM Proteins; D000072198:ADAM17 Protein; C000606462:ADAM17 protein, human