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Molecular Cancer
Published in: Molecular Cancer 1/2014

Open Access 01-12-2014 | Research

ADAM17 mediates OSCC development in an orthotopic murine model

Authors: Fernando Moreira Simabuco, Rebeca Kawahara, Sami Yokoo, Daniela C Granato, Lucas Miguel, Michelle Agostini, Annelize ZB Aragão, Romênia R Domingues, Isadora L Flores, Carolina CS Macedo, Ricardo Della Coletta, Edgard Graner, Adriana Franco Paes Leme

Published in: Molecular Cancer | Issue 1/2014

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Abstract

Background

ADAM17 is one of the main sheddases of the cells and it is responsible for the cleavage and the release of ectodomains of important signaling molecules, such as EGFR ligands. Despite the known crosstalk between ADAM17 and EGFR, which has been considered a promising targeted therapy in oral squamous cell carcinoma (OSCC), the role of ADAM17 in OSCC development is not clear.

Method

In this study the effect of overexpressing ADAM17 in cell migration, viability, adhesion and proliferation was comprehensively appraised in vitro. In addition, the tumor size, tumor proliferative activity, tumor collagenase activity and MS-based proteomics of tumor tissues have been evaluated by injecting tumorigenic squamous carcinoma cells (SCC-9) overexpressing ADAM17 in immunodeficient mice.

Results

The proteomic analysis has effectively identified a total of 2,194 proteins in control and tumor tissues. Among these, 110 proteins have been down-regulated and 90 have been up-regulated in tumor tissues. Biological network analysis has uncovered that overexpression of ADAM17 regulates Erk pathway in OSCC and further indicates proteins regulated by the overexpression of ADAM17 in the respective pathway. These results are also supported by the evidences of higher viability, migration, adhesion and proliferation in SCC-9 or A431 cells in vitro along with the increase of tumor size and proliferative activity and higher tissue collagenase activity as an outcome of ADAM17 overexpression.

Conclusion

These findings contribute to understand the role of ADAM17 in oral cancer development and as a potential therapeutic target in oral cancer. In addition, our study also provides the basis for the development of novel and refined OSCC-targeting approaches.
Appendix
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Literature
1.
Murphy G: The ADAMs: signalling scissors in the tumour microenvironment. Nat Rev Cancer. 2008, 8: 929-941.CrossRefPubMed
2.
3.
Edwards DR, Handsley MM, Pennington CJ: The ADAM metalloproteinases. Mol Aspects Med. 2008, 29: 258-289. 10.1016/j.mam.2008.08.001CrossRefPubMed
4.
Duffy MJ, McKiernan E, O’Donovan N, McGowan PM: Role of ADAMs in cancer formation and progression. Clin Cancer Res. 2009, 15: 1140-1144. 10.1158/1078-0432.CCR-08-1585CrossRefPubMed
5.
Blobel CP: ADAMs: key components in EGFR signalling and development. Nat Rev Mol Cell Biol. 2005, 6: 32-43. 10.1038/nrm1548CrossRefPubMed
6.
Sheu JJ-C, Hua C-H, Wan L, Lin Y-J, Lai M-T, Tseng H-C, Jinawath N, Tsai M-H, Chang N-W, Lin C-F, Lin C-C, Hsieh L-J, Wang T-L, Shih I-M, Tsai F-J: Functional genomic analysis identified epidermal growth factor receptor activation as the most common genetic event in oral squamous cell carcinoma. Cancer Res. 2009, 69: 2568-2576. 10.1158/0008-5472.CAN-08-3199CrossRefPubMed
7.
Bonner J, Harari PM, Giralt J, Azarnia N, Shin DM, Cohen RB, Jones CU, Sur R, Raben D, Jassem J, Ove R, Kies MS, Baselga J, Youssoufian H, Amellal N, Rowinsky EK, Ang KK: Radiotherapy plus cetuximab for squamous-cell carcinoma of the head and neck. N Engl J Med. 2006, 354: 567-578. 10.1056/NEJMoa053422CrossRefPubMed
8.
Huang S, O Sullivan B: Oral cancer: current role of radiotherapy and chemotherapy. Med Oral Patol Oral y Cir Bucal. 2013, 18: e233-e240.CrossRef
9.
Petersen PE: The world oral health report 2003: continuous improvement of oral health in the 21st century–the approach of the WHO global oral health programme. Community Dent Oral Epidemiol. 2003, 31 (Suppl 1): 3-23.CrossRefPubMed
10.
Gschwind A, Hart S, Fischer O, Ullrich A: TACE cleavage of proamphiregulin regulates GPCR-induced proliferation and motility of cancer cells. EMBO J. 2003, 22: 2411-2421. 10.1093/emboj/cdg231PubMedCentralCrossRefPubMed
11.
Sobral LM, Bufalino A, Lopes M, Graner E, Salo T, Coletta RD: Myofibroblasts in the stroma of oral cancer promote tumorigenesis via secretion of activin A. Oral Oncol. 2011, 47: 840-846. 10.1016/j.oraloncology.2011.06.011CrossRefPubMed
12.
Paes Leme AF, Sherman NE, Smalley DM, Sizukusa LO, Oliveira AK, Menezes MC, Fox JW, Serrano SMT: Hemorrhagic activity of HF3, a snake venom metalloproteinase: insights from the proteomic analysis of mouse skin and blood plasma. J Proteome Res. 2012, 11: 279-291. 10.1021/pr2006439CrossRefPubMed
13.
Rappsilber J, Mann M, Ishihama Y: Protocol for micro-purification, enrichment, pre-fractionation and storage of peptides for proteomics using StageTips. Nat Protoc. 2007, 2: 1896-1906. 10.1038/nprot.2007.261CrossRefPubMed
14.
Aragão AZB, Belloni M, Simabuco FM, Zanetti MR, Yokoo S, Domingues RR, Kawahara R, Pauletti B, Gonçalves A, Agostini M, Graner E, Coletta RD, Fox JW, Leme AFP: Novel processed form of syndecan-1 shed from SCC-9 cells plays a role in cell migration. PLoS One. 2012, 7: e43521- 10.1371/journal.pone.0043521PubMedCentralCrossRefPubMed
15.
Cox J, Mann M: MaxQuant enables high peptide identification rates, individualized p.p.b.-range mass accuracies and proteome-wide protein quantification. Nat Biotechnol. 2008, 26: 1367-1372. 10.1038/nbt.1511CrossRefPubMed
16.
Cox J, Neuhauser N, Michalski A, Scheltema R, Olsen JV, Mann M: Andromeda: a peptide search engine integrated into the MaxQuant environment. J Proteome Res. 2011, 10: 1794-1805. 10.1021/pr101065jCrossRefPubMed
17.
McIlwain DR, Lang PA, Maretzky T, Hamada K, Ohishi K, Maney SK, Berger T, Murthy A, Duncan G, Xu HC, Lang KS, Häussinger D, Wakeham A, Itie-Youten A, Khokha R, Ohashi PS, Blobel CP, Mak TW: iRhom2 Regulation of TACE controls TNF-mediated protection against listeria and responses to LPS. Science. 2012, 335: 229-232. 10.1126/science.1214448PubMedCentralCrossRefPubMed
18.
Le Gall SM, Maretzky T, Issuree PD, Niu X-D, Reiss K, Saftig P, Khokha R, Lundell D, Blobel CP: ADAM17 is regulated by a rapid and reversible mechanism that controls access to its catalytic site. J Cell Sci. 2010, 123 (Pt 22): 3913-3922.PubMedCentralCrossRefPubMed
19.
Aragão AZB, Nogueira MLC, Granato DC, Simabuco FM, Honorato RV, Hoffman Z, Yokoo S, Laurindo FRM, Squina FM, Zeri ACM, Oliveira PSL, Sherman NE, Paes Leme AF: Identification of novel interaction between ADAM17 (a disintegrin and metalloprotease 17) and thioredoxin-1. J Biol Chem. 2012, 287: 43071-43082. 10.1074/jbc.M112.364513PubMedCentralCrossRefPubMed
20.
Paes Leme AF, Kitano ES, Furtado MF, Valente RH, Camargo ACM, Ho PL, Fox JW, Serrano SMT: Analysis of the subproteomes of proteinases and heparin-binding toxins of eight bothrops venoms. Proteomics. 2009, 9: 733-745. 10.1002/pmic.200800484CrossRefPubMed
21.
Najy AJ, Day KC, Day ML: ADAM15 supports prostate cancer metastasis by modulating tumor cell-endothelial cell interaction. Cancer Res. 2008, 68: 1092-1099. 10.1158/0008-5472.CAN-07-2432CrossRefPubMed
22.
Maretzky T, Evers A, Zhou W, Swendeman SL, Wong P-M, Rafii S, Reiss K, Blobel CP: Migration of growth factor-stimulated epithelial and endothelial cells depends on EGFR transactivation by ADAM17. Nat Commun. 2011, 2: 229-PubMedCentralCrossRefPubMed
23.
24.
Das S, Czarnek M, Bzowska M, Mężyk-Kopeć R, Stalińska K, Wyroba B, Sroka J, Jucha J, Deneka D, Stokłosa P, Ogonek J, Swartz MA, Madeja Z, Bereta J: ADAM17 silencing in mouse colon carcinoma cells: the effect on tumoricidal cytokines and angiogenesis. PLoS One. 2012, 7: e50791- 10.1371/journal.pone.0050791PubMedCentralCrossRefPubMed
25.
Lin P, Sun X, Feng T, Zou H, Jiang Y, Liu Z, Zhao D, Yu X: ADAM17 regulates prostate cancer cell proliferation through mediating cell cycle progression by EGFR/PI3K/AKT pathway. Mol Cell Biochem. 2012, 359: 235-243. 10.1007/s11010-011-1018-8CrossRefPubMed
26.
Perna AF, Sepe I, Lanza D, Capasso R, Zappavigna S, Capasso G, Caraglia M, Ingrosso D: Hydrogen sulfide reduces cell adhesion and relevant inflammatory triggering by preventing ADAM17-dependent TNF-α activation. J Cell Biochem. 2013, 114: 1536-1548. 10.1002/jcb.24495CrossRefPubMed
27.
Rocks N, Estrella C, Paulissen G, Quesada-Calvo F, Gilles C, Guéders MM, Crahay C, Foidart J-M, Gosset P, Noel A, Cataldo DD: The metalloproteinase ADAM-12 regulates bronchial epithelial cell proliferation and apoptosis. Cell Prolif. 2008, 41: 988-1001. 10.1111/j.1365-2184.2008.00557.xCrossRefPubMed
28.
Ge L, Baskic D, Basse P, Vujanovic L, Unlu S, Yoneyama T, Vujanovic A, Han J, Bankovic D, Szczepanski MJ, Hunt JL, Herberman RB, Gollin SM, Ferris RL, Whiteside TL, Myers EN, Vujanovic NL: Sheddase activity of tumor necrosis factor-alpha converting enzyme is increased and prognostically valuable in head and neck cancer. Cancer Epidemiol Biomarkers Prev. 2009, 18: 2913-2922. 10.1158/1055-9965.EPI-08-0898PubMedCentralCrossRefPubMed
29.
Stokes A, Joutsa J, Ala-Aho R, Pitchers M, Pennington CJ, Martin C, Premachandra DJ, Okada Y, Peltonen J, Grénman R, James H, Edwards DR, Kähäri V-M: Expression profiles and clinical correlations of degradome components in the tumor microenvironment of head and neck squamous cell carcinoma. Clin Cancer Res. 2010, 16: 2022-2035. 10.1158/1078-0432.CCR-09-2525CrossRefPubMed
30.
Kornfeld J-W, Meder S, Wohlberg M, Friedrich RE, Rau T, Riethdorf L, Löning T, Pantel K, Riethdorf S: Overexpression of TACE and TIMP3 mRNA in head and neck cancer: association with tumour development and progression. Br J Cancer. 2011, 104: 138-145. 10.1038/sj.bjc.6606017PubMedCentralCrossRefPubMed
31.
Hinsley EE, Hunt S, Hunter KD, Whawell S a, Lambert DW: Endothelin-1 stimulates motility of head and neck squamous carcinoma cells by promoting stromal-epithelial interactions. Int J Cancer. 2012, 130: 40-47. 10.1002/ijc.25968CrossRefPubMed
32.
Yu C-C, Tsai L-L, Wang M-L, Yu C-H, Lo W-L, Chang Y-C, Chiou G-Y, Chou M-Y, Chiou S-H S-H: miR145 Targets the SOX9/ADAM17 axis to inhibit tumor-initiating cells and IL-6-mediated paracrine effects in head and neck cancer. Cancer Res. 2013, 71: 3425-3440.CrossRef
33.
M Andrade L, Geraldo JM: Nucleoplasmic calcium buffering sensitizes human squamous cell carcinoma to anticancer therapy. J Cancer Sci Ther. 2012, 04: 131-139.CrossRef
34.
Steelman LS, Franklin RA, Abrams SL, Chappell W, Kempf CR, Bäsecke J, Stivala F, Donia M, Fagone P, Nicoletti F, Libra M, Ruvolo P, Ruvolo V, Evangelisti C, Martelli AM, McCubrey JA: Roles of the Ras/Raf/MEK/ERK pathway in leukemia therapy. Leukemia. 2011, 25: 1080-1094. 10.1038/leu.2011.66CrossRefPubMed
35.
Roskoski R: ERK1/2 MAP kinases: structure, function, and regulation. Pharmacol Res. 2012, 66: 105-143. 10.1016/j.phrs.2012.04.005CrossRefPubMed
36.
Da Silva SD, Ferlito A, Takes RP, Brakenhoff RH, Valentin MD, Woolgar JA, Bradford CR, Rodrigo JP, Rinaldo A, Hier MP, Kowalski LP: Advances and applications of oral cancer basic research. Oral Oncol. 2011, 47: 783-791. 10.1016/j.oraloncology.2011.07.004CrossRefPubMed
37.
Wang D, Su L, Huang D, Zhang H, Shin DM, Chen ZG: Downregulation of E-Cadherin enhances proliferation of head and neck cancer through transcriptional regulation of EGFR. Mol Cancer. 2011, 10: 116- 10.1186/1476-4598-10-116PubMedCentralCrossRefPubMed
38.
Guinea-Viniegra J, Zenz R, Scheuch H, Jiménez M, Bakiri L, Petzelbauer P, Wagner EF: Differentiation-induced skin cancer suppression by FOS, p53, and TACE/ADAM17. J Clin Invest. 2012, 122: 2898-2910. 10.1172/JCI63103PubMedCentralCrossRefPubMed
39.
Baldwin AS: Regulation of cell death and autophagy by IKK and NF-κB: critical mechanisms in immune function and cancer. Immunol Rev. 2012, 246: 327-345. 10.1111/j.1600-065X.2012.01095.xCrossRefPubMed
40.
Page A, Cascallana JL, Casanova ML, Navarro M, Alameda JP, Pérez P, Bravo A, Ramírez A: IKKβ overexpression leads to pathologic lesions in stratified epithelia and exocrine glands and to tumoral transformation of oral epithelia. Mol Cancer Res. 2011, 9: 1329-1338. 10.1158/1541-7786.MCR-11-0168CrossRefPubMed
41.
Lu K-W, Tsai M-L, Chen J-C, Hsu S-C, Hsia T-C, Lin M-W, Huang A-C, Chang Y-H, Ip S-W, Lu H-F, Chung J-G: Gypenosides inhibited invasion and migration of human tongue cancer SCC4 cells through down-regulation of NFkappaB and matrix metalloproteinase-9. Anticancer Res. 2008, 28: 1093-1099.PubMed
42.
Kwon H-K, Hwang J-S, So J-S, Lee C-G, Sahoo A, Ryu J-H, Jeon WK, Ko BS, Im C-R, Lee SH, Park ZY, Im S-H: Cinnamon extract induces tumor cell death through inhibition of NFkappaB and AP1. BMC Cancer. 2010, 10: 392- 10.1186/1471-2407-10-392PubMedCentralCrossRefPubMed
43.
Bouwmeester T, Bauch A, Ruffner H, Angrand P-O, Bergamini G, Croughton K, Cruciat C, Eberhard D, Gagneur J, Ghidelli S, Hopf C, Huhse B, Mangano R, Michon A-M, Schirle M, Schlegl J, Schwab M, Stein MA, Bauer A, Casari G, Drewes G, Gavin A-C, Jackson DB, Joberty G, Neubauer G, Rick J, Kuster B, Superti-Furga G: A physical and functional map of the human TNF-alpha/NF-kappa B signal transduction pathway. Nat Cell Biol. 2004, 6: 97-105. 10.1038/ncb1086CrossRefPubMed
44.
Prenzel N, Zwick E, Daub H, Leserer M, Abraham R, Wallasch C, Ullrich A: EGF receptor transactivation by G-protein-coupled receptors requires metalloproteinase cleavage of proHB-EGF. Nature. 1999, 402: 884-888.PubMed
45.
Zhang Q, Thomas SM, Xi S, Smithgall TE, Siegfried JM, Kamens J, Gooding WE, Grandis JR: SRC family kinases mediate epidermal growth factor receptor ligand cleavage, proliferation, and invasion of head and neck cancer cells. Cancer Res. 2004, 64: 6166-6173. 10.1158/0008-5472.CAN-04-0504CrossRefPubMed
46.
McCubrey JA, Steelman LS, Chappell WH, Abrams SL, Wong EWT, Chang F, Lehmann B, Terrian DM, Milella M, Tafuri A, Stivala F, Libra M, Basecke J, Evangelisti C, Martelli AM, Franklin RA: Roles of the Raf/MEK/ERK pathway in cell growth, malignant transformation and drug resistance. Biochim Biophys Acta. 2007, 1773: 1263-1284. 10.1016/j.bbamcr.2006.10.001PubMedCentralCrossRefPubMed
47.
Ma L, Lan F, Zheng Z, Xie F, Wang L, Liu W, Han J, Zheng F, Xie Y, Huang Q: Epidermal growth factor (EGF) and interleukin (IL)-1β synergistically promote ERK1/2-mediated invasive breast ductal cancer cell migration and invasion. Mol Cancer. 2012, 11: 79- 10.1186/1476-4598-11-79PubMedCentralCrossRefPubMed
48.
Odenbach J, Wang X, Cooper S, Chow FL, Oka T, Lopaschuk G, Kassiri Z, Fernandez-Patron C: MMP-2 mediates angiotensin II-induced hypertension under the transcriptional control of MMP-7 and TACE. Hypertension. 2011, 57: 123-130. 10.1161/HYPERTENSIONAHA.110.159525CrossRefPubMed
49.
Wang X, Oka T, Chow FL, Cooper SB, Odenbach J, Lopaschuk GD, Kassiri Z, Fernandez-Patron C: Tumor necrosis factor-alpha-converting enzyme is a key regulator of agonist-induced cardiac hypertrophy and fibrosis. Hypertension. 2009, 54: 575-582. 10.1161/HYPERTENSIONAHA.108.127670CrossRefPubMed
50.
Xiao L-J, Lin P, Lin F, Liu X, Qin W, Zou H-F, Guo L, Liu W, Wang S-J, Yu X-G: ADAM17 targets MMP-2 and MMP-9 via EGFR-MEK-ERK pathway activation to promote prostate cancer cell invasion. Int J Oncol. 2012, 40: 1714-1724.PubMed
Metadata
Title
ADAM17 mediates OSCC development in an orthotopic murine model
Authors
Fernando Moreira Simabuco
Rebeca Kawahara
Sami Yokoo
Daniela C Granato
Lucas Miguel
Michelle Agostini
Annelize ZB Aragão
Romênia R Domingues
Isadora L Flores
Carolina CS Macedo
Ricardo Della Coletta
Edgard Graner
Adriana Franco Paes Leme
Publication date
01-12-2014
Publisher
BioMed Central
Published in
Molecular Cancer / Issue 1/2014
Electronic ISSN: 1476-4598
DOI
https://doi.org/10.1186/1476-4598-13-24

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