title: ADAM-17 associated with CD44 cleavage and metastasis in oral squamous cell carcinoma.
abstract: ADAM-17 (a disintegrin and metalloproteinase 17) is a membrane-anchored protein, which can cleave the ectodomain in a variety of transmembrane proteins. In the in vitro experiments with tumor cells, ADAM-17 is reported to cleave CD44, an adhesion molecule that interacts with hyaluronic acid, to promote tumor cell migration. In the present study, we examined ADAM-17 expression and CD44 cleavage in specimens from 50 patients diagnosed to have oral squamous cell carcinoma (SCC). Each specimen was divided into two pieces, one was studied by immunohistochemistry and the other was subjected to a Western blot. By coordinating the results of both analyses, ADAM-17 expression was evaluated to be high in 23 cases (46%). When CD44 cleavage was also studied by immunohistochemical staining as well as with Western blotting, CD44 cleavage was judged to be positive in 29 cases (58%). When the ADAM-17 expression level was compared with the CD44 cleavage state, most of the cases expressing high levels of ADAM-17 (87%) showed positive CD44 cleavage. The level of ADAM-17 expression was significantly correlated to the nodal metastasis and local recurrence in oral SCC. Our findings suggest that ADAM-17 is involved in CD44 cleavage and contributes to tumor progression in oral SCC.
authors.affiliation: Department of Oral and Maxillofacial Surgery, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto 860-8556, Japan.
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Takamune
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Ikebe
authors.forename: Osamu
authors.initials: O
authors.lastname: Nagano
authors.forename: Hideki
authors.initials: H
authors.lastname: Nakayama
authors.forename: Kazutoshi
authors.initials: K
authors.lastname: Ota
authors.forename: Takehisa
authors.initials: T
authors.lastname: Obayashi
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Saya
authors.forename: Masanori
authors.initials: M
authors.lastname: Shinohara
mesh_terms: D051722:ADAM Proteins / Q000032:analysis* / Q000502:physiology; D000072198:ADAM17 Protein; D000368:Aged; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000737:chemistry / Q000473:pathology*; D005260:Female; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000737:chemistry / Q000473:pathology*; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local
chemical_list: D018960:Hyaluronan Receptors; D051722:ADAM Proteins; D000072198:ADAM17 Protein; C000606462:ADAM17 protein, human