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Published in: Virchows Archiv 2/2007

01-02-2007 | Original Article

ADAM-17 associated with CD44 cleavage and metastasis in oral squamous cell carcinoma

Authors: Yasuo Takamune, Tetsuro Ikebe, Osamu Nagano, Hideki Nakayama, Kazutoshi Ota, Takehisa Obayashi, Hideyuki Saya, Masanori Shinohara

Published in: Virchows Archiv | Issue 2/2007

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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.
Literature
1.
go back to reference Black RA, Rauch CT, Kozlosky CJ, Peschon JJ, Slack JL, Wolfson MF, Castner BJ, Stocking KL, Reddy P, Srinivasan S, Nelson N, Boiani N, Schooley KA, Gerhart M, Davis R, Fitzner JN, Johnson RS, Paxton RJ, March CJ, Cerretti DP (1997) A metalloproteinase disintegrin that releases tumour-necrosis factor-α from cells. Nature 385:729–733PubMedCrossRef Black RA, Rauch CT, Kozlosky CJ, Peschon JJ, Slack JL, Wolfson MF, Castner BJ, Stocking KL, Reddy P, Srinivasan S, Nelson N, Boiani N, Schooley KA, Gerhart M, Davis R, Fitzner JN, Johnson RS, Paxton RJ, March CJ, Cerretti DP (1997) A metalloproteinase disintegrin that releases tumour-necrosis factor-α from cells. Nature 385:729–733PubMedCrossRef
2.
go back to reference Blanchot-Jossic F, Jarry A, Masson D, Bach-Ngohou K, Paineau J, Denis MG, Laboisse CL, Mosnier JF (2005) Up-regulated expression of ADAM-17 in human colon carcinoma: co-expression with EGFR in neoplastic and endothelial cells. J Pathol 207:156–163PubMedCrossRef Blanchot-Jossic F, Jarry A, Masson D, Bach-Ngohou K, Paineau J, Denis MG, Laboisse CL, Mosnier JF (2005) Up-regulated expression of ADAM-17 in human colon carcinoma: co-expression with EGFR in neoplastic and endothelial cells. J Pathol 207:156–163PubMedCrossRef
3.
go back to reference Borrell-Pages M, Rojo F, Albanell J, Baselga J, Arribas J (2003) TACE is required for the activation of the EGFR by TGF-α in tumors. EMBO J 22:1114–1124PubMedCrossRef Borrell-Pages M, Rojo F, Albanell J, Baselga J, Arribas J (2003) TACE is required for the activation of the EGFR by TGF-α in tumors. EMBO J 22:1114–1124PubMedCrossRef
4.
go back to reference De Marzo AM, Bradshaw C, Sauvageot J, Epstein JI, Miller GJ (1998) CD44 and CD44v6 downregulation in clinical prostatic carcinoma: relation to Gleason grade and cytoarchitecture. J Hered 34:162–168 De Marzo AM, Bradshaw C, Sauvageot J, Epstein JI, Miller GJ (1998) CD44 and CD44v6 downregulation in clinical prostatic carcinoma: relation to Gleason grade and cytoarchitecture. J Hered 34:162–168
5.
go back to reference Fabre-Lafay S, Garrido-Urbani S, Reymond N, Goncalves A, Dubreuil P, Lopez M (2005) Nectin-4, a new serological breast cancer marker, is a substrate for tumor necrosis factor-a-converting enzyme (TACE)/ADAM-17. J Biol Chem 280:19543–19550PubMedCrossRef Fabre-Lafay S, Garrido-Urbani S, Reymond N, Goncalves A, Dubreuil P, Lopez M (2005) Nectin-4, a new serological breast cancer marker, is a substrate for tumor necrosis factor-a-converting enzyme (TACE)/ADAM-17. J Biol Chem 280:19543–19550PubMedCrossRef
6.
go back to reference Fonseca I, Pereira T, Rosa-Santos J, Soares J (2001) Expression of CD44 isoforms in squamous cell carcinoma of the border of the tongue: a correlation with histological grade, pattern of stromal invasion, and cell differentiation. J Surg Oncol 76:115–120PubMedCrossRef Fonseca I, Pereira T, Rosa-Santos J, Soares J (2001) Expression of CD44 isoforms in squamous cell carcinoma of the border of the tongue: a correlation with histological grade, pattern of stromal invasion, and cell differentiation. J Surg Oncol 76:115–120PubMedCrossRef
7.
go back to reference Gao AC, Lou W, Dong JT, Isaacs JT (1997) CD44 is a metastasis suppressor gene for prostatic cancer located on human chromosome 11p13. Cancer Res 57:846–849PubMed Gao AC, Lou W, Dong JT, Isaacs JT (1997) CD44 is a metastasis suppressor gene for prostatic cancer located on human chromosome 11p13. Cancer Res 57:846–849PubMed
8.
go back to reference Guo YJ, Liu G, Wang X, Jin D, Wu M, Ma J, Sy MS (1994) Potential use of soluble CD44 in serum as indicator of tumor burden and metastasis in patients with gastric or colon cancer. Cancer Res 54:422–426PubMed Guo YJ, Liu G, Wang X, Jin D, Wu M, Ma J, Sy MS (1994) Potential use of soluble CD44 in serum as indicator of tumor burden and metastasis in patients with gastric or colon cancer. Cancer Res 54:422–426PubMed
9.
go back to reference Kajita M, Itoh Y, Chiba T, Mori H, Okada A, Kinoh H, Seiki M (2001) Membrane-type 1 matrix metalloproteinase cleaves CD44 and promotes cell migration. J Cell Biol 153:893–904PubMedCrossRef Kajita M, Itoh Y, Chiba T, Mori H, Okada A, Kinoh H, Seiki M (2001) Membrane-type 1 matrix metalloproteinase cleaves CD44 and promotes cell migration. J Cell Biol 153:893–904PubMedCrossRef
10.
go back to reference Karan D, Lin FC, Bryan M, Ringel J, Moniaux N, Lin MF, Batra SK (2003) Expression of ADAMs (a disintegrin and metalloproteases) and TIMP-3 (tissue inhibitor of metalloproteinase-3) in human prostatic adenocarcinoma. Int J Oncol 23:1365–1371PubMed Karan D, Lin FC, Bryan M, Ringel J, Moniaux N, Lin MF, Batra SK (2003) Expression of ADAMs (a disintegrin and metalloproteases) and TIMP-3 (tissue inhibitor of metalloproteinase-3) in human prostatic adenocarcinoma. Int J Oncol 23:1365–1371PubMed
11.
go back to reference Moss ML, Jin SLC, Milla ME, Burkhart W, Carter HL, Chen WJ, Clay WC, Didsbury JR, Hassler D, Hoffman CR, Kost TA, Lambert MH, Leesnitzer MA, McCauley P, McGeehan G, Mitchell J, Moyer M, Pahel G, Rocque W, Overton LK, Schoenen F, Seaton T, Su JL, Warner J, Willard D, Becherer JD (1997) Cloning of a disintegrin metalloproteinase that processes precursor tumour-necrosis factor-α. Nature 385:733–736PubMedCrossRef Moss ML, Jin SLC, Milla ME, Burkhart W, Carter HL, Chen WJ, Clay WC, Didsbury JR, Hassler D, Hoffman CR, Kost TA, Lambert MH, Leesnitzer MA, McCauley P, McGeehan G, Mitchell J, Moyer M, Pahel G, Rocque W, Overton LK, Schoenen F, Seaton T, Su JL, Warner J, Willard D, Becherer JD (1997) Cloning of a disintegrin metalloproteinase that processes precursor tumour-necrosis factor-α. Nature 385:733–736PubMedCrossRef
12.
go back to reference Nagano O, Murakami D, Hartmann D, de Strooper B, Saftig P, Iwatsubo T, Nakajima M, Shinohara M, Saya H (2004) Cell-matrix interaction via CD44 is independently regulated by different metalloproteinases activated in response to extracellular Ca2+ influx and PKC activation. J Cell Biol 165:893–902PubMedCrossRef Nagano O, Murakami D, Hartmann D, de Strooper B, Saftig P, Iwatsubo T, Nakajima M, Shinohara M, Saya H (2004) Cell-matrix interaction via CD44 is independently regulated by different metalloproteinases activated in response to extracellular Ca2+ influx and PKC activation. J Cell Biol 165:893–902PubMedCrossRef
13.
go back to reference Nakamura H, Suenaga N, Taniwaki K, Matsuki H, Yonezawa K, Fujii M, Okada Y, Seiki M (2004) Constitutive and induced CD44 shedding by ADAM-like proteases and membrane-type 1 matrix metalloproteinase. Cancer Res 64:876–882PubMedCrossRef Nakamura H, Suenaga N, Taniwaki K, Matsuki H, Yonezawa K, Fujii M, Okada Y, Seiki M (2004) Constitutive and induced CD44 shedding by ADAM-like proteases and membrane-type 1 matrix metalloproteinase. Cancer Res 64:876–882PubMedCrossRef
14.
go back to reference Okamoto I, Kawano Y, Tsuiki H, Sasaki J, Nakao M, Matsumoto M, Suga M, Ando M, Nakajima M, Saya H (1999) CD44 cleavage induced by membrane-associated metalloprotease plays a critical role in tumor cell migration. Oncogene 18:1435–1446PubMedCrossRef Okamoto I, Kawano Y, Tsuiki H, Sasaki J, Nakao M, Matsumoto M, Suga M, Ando M, Nakajima M, Saya H (1999) CD44 cleavage induced by membrane-associated metalloprotease plays a critical role in tumor cell migration. Oncogene 18:1435–1446PubMedCrossRef
15.
go back to reference Okamoto I, Tsuiki H, Kenyon LC, Godwin AK, Emlet DR, Holgado-Madruga M, Lanham IS, Joynes CJ, Vo KT, Guha A, Matsumoto M, Ushio Y, Saya H, Wong AJ (2002) Proteolytic cleavage of the CD44 adhesion molecule in multiple human tumors. Am J Pathol 160:441–447PubMed Okamoto I, Tsuiki H, Kenyon LC, Godwin AK, Emlet DR, Holgado-Madruga M, Lanham IS, Joynes CJ, Vo KT, Guha A, Matsumoto M, Ushio Y, Saya H, Wong AJ (2002) Proteolytic cleavage of the CD44 adhesion molecule in multiple human tumors. Am J Pathol 160:441–447PubMed
16.
go back to reference Ponta H, Sherman L, Herrlich PA (2003) CD44: from adhesion molecules to signalling regulators. Nature Rev Mol Cell Biol 4:33–45CrossRef Ponta H, Sherman L, Herrlich PA (2003) CD44: from adhesion molecules to signalling regulators. Nature Rev Mol Cell Biol 4:33–45CrossRef
17.
go back to reference Sato S, Miyauchi M, Takekoshi T, Zhao M, Kudo Y, Ogawa I, Kitagawa S, Fujita M, Takata T (2000) Reduced expression of CD44 variant 9 is related to lymph node metastasis and poor survival in squamous cell carcinoma of tongue. Oral Oncol 36:545–549PubMedCrossRef Sato S, Miyauchi M, Takekoshi T, Zhao M, Kudo Y, Ogawa I, Kitagawa S, Fujita M, Takata T (2000) Reduced expression of CD44 variant 9 is related to lymph node metastasis and poor survival in squamous cell carcinoma of tongue. Oral Oncol 36:545–549PubMedCrossRef
18.
go back to reference Seals DF, Courtneidge SA (2003) The ADAMs family of metalloproteinases: multidomain proteins with multiple functions. Genes Dev 17:7–30PubMedCrossRef Seals DF, Courtneidge SA (2003) The ADAMs family of metalloproteinases: multidomain proteins with multiple functions. Genes Dev 17:7–30PubMedCrossRef
19.
go back to reference Sheen-Chen SM, Chen WJ, Eng HL, Sheen CC, Chou FF, Cheng YF (1999) Evaluation of the prognostic value of serum soluble CD44 in patients with breast cancer. Cancer Invest 17:581–585PubMedCrossRef Sheen-Chen SM, Chen WJ, Eng HL, Sheen CC, Chou FF, Cheng YF (1999) Evaluation of the prognostic value of serum soluble CD44 in patients with breast cancer. Cancer Invest 17:581–585PubMedCrossRef
20.
go back to reference Shtivelman E, Bishop J (1991) Expression of CD44 is repressed in neuroblastoma cells. Mol Cell Biol 11:5446–5453PubMed Shtivelman E, Bishop J (1991) Expression of CD44 is repressed in neuroblastoma cells. Mol Cell Biol 11:5446–5453PubMed
21.
go back to reference Tanaka Y, Miyamoto S, Suzuki SO, Oki E, Yagi H, Sonoda K, Yamazaki A, Mizushima H, Maehara Y, Mekada E, Nakano H (2005) Clinical significance of heparin-binding epidermal growth factor-like growth factor and a disintegrin and metalloprotease 17 expression in human ovarian cancer. Clin Cancer Res 11:4783–4792PubMedCrossRef Tanaka Y, Miyamoto S, Suzuki SO, Oki E, Yagi H, Sonoda K, Yamazaki A, Mizushima H, Maehara Y, Mekada E, Nakano H (2005) Clinical significance of heparin-binding epidermal growth factor-like growth factor and a disintegrin and metalloprotease 17 expression in human ovarian cancer. Clin Cancer Res 11:4783–4792PubMedCrossRef
Metadata
Title
ADAM-17 associated with CD44 cleavage and metastasis in oral squamous cell carcinoma
Authors
Yasuo Takamune
Tetsuro Ikebe
Osamu Nagano
Hideki Nakayama
Kazutoshi Ota
Takehisa Obayashi
Hideyuki Saya
Masanori Shinohara
Publication date
01-02-2007
Publisher
Springer-Verlag
Published in
Virchows Archiv / Issue 2/2007
Print ISSN: 0945-6317
Electronic ISSN: 1432-2307
DOI
https://doi.org/10.1007/s00428-006-0350-y

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