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BMC Cancer
Published in: BMC Cancer 1/2008

Open Access 01-12-2008 | Research article

Suppression of local invasion of ameloblastoma by inhibition of matrix metalloproteinase-2 in vitro

Authors: Anxun Wang, Bin Zhang, Hongzhang Huang, Leitao Zhang, Donglin Zeng, Qian Tao, Jianguang Wang, Chaobin Pan

Published in: BMC Cancer | Issue 1/2008

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Abstract

Background

Ameloblastomas are odontogenic neoplasms characterized by local invasiveness. This study was conducted to address the role of matrix metalloproteinase-2 (MMP-2) in the invasiveness of ameloblastomas.

Methods

Plasmids containing either MMP-2 siRNA or tissue inhibitor of metalloproteinase-2 (TIMP-2) cDNA were created and subsequently transfected into primary ameloblastoma cells. Zymography, RT-PCR, and Western blots were used to assess MMP-2 activity and expression of MMP-2 and TIMP-2, as well as protein levels.

Results

Primary cultures of ameloblastoma cells expressed cytokeratin (CK) 14 and 16, and MMP-2, but only weakly expressed CK18 and vimentin. MMP-2 mRNA and protein levels were significantly inhibited by RNA interference (P < 0.05). Both MMP-2 siRNA and TIMP-2 overexpression inhibited MMP-2 activity and the in vitro invasiveness of ameloblastoma.

Conclusion

These results indicate that inhibition of MMP-2 activity suppresses the local invasiveness of ameloblastoma cells. This mechanism may serve as a novel therapeutic target in ameloblastomas pursuant to additional research.
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Literature
1.
Gruica B, Stauffer E, Buser D, Bornstein M: Ameloblastoma of the follicular, plexiform, and acanthomatous type in the maxillary sinus: a case report. Quintessence Int. 2003, 34 (4): 311-314.PubMed
2.
Junquera L, Ascani G, Vicente JC, Garcia-Consuegra L, Roig P: Ameloblastoma revisited. Ann Otol Rhinol Laryngol. 2003, 112 (12): 1034-1039.CrossRefPubMed
3.
Heikinheimo K, Jee KJ, Niini T, Aalto Y, Happonen RP, Leivo I, Knuutila S: Gene expression profiling of ameloblastoma and human tooth germ by means of a cDNA microarray. J Dent Res. 2002, 81 (8): 525-530.CrossRefPubMed
4.
Kumamoto H: Molecular pathology of odontogenic tumors. J Oral Pathol Med. 2006, 35 (2): 65-74. 10.1111/j.1600-0714.2006.00380.x.CrossRefPubMed
5.
Liotta LA, Stetler-Stevenson WG: Metalloproteinases and cancer invasion. Semin Cancer Biol. 1990, 1 (2): 99-106.PubMed
6.
Stamenkovic I: Extracellular matrix remodelling: the role of matrix metalloproteinases. J Pathol. 2003, 200 (4): 448-464. 10.1002/path.1400.CrossRefPubMed
7.
Birkedal-Hansen H, Moore WG, Bodden MK, Windsor LJ, Birkedal-Hansen B, DeCarlo A, Engler JA: Matrix metalloproteinases: a review. Crit Rev Oral Biol Med. 1993, 4 (2): 197-250.PubMed
8.
Nagase H: Activation mechanisms of matrix metalloproteinases. Biol Chem. 1997, 378 (3-4): 151-160.PubMed
9.
Coussens LM, Werb Z: Matrix metalloproteinases and the development of cancer. Chem Biol. 1996, 3 (11): 895-904. 10.1016/S1074-5521(96)90178-7.CrossRefPubMed
10.
Stetler-Stevenson WG, Hewitt R, Corcoran M: Matrix metalloproteinases and tumor invasion: from correlation and causality to the clinic. Semin Cancer Biol. 1996, 7 (3): 147-154. 10.1006/scbi.1996.0020.CrossRefPubMed
11.
Kumamoto H, Yamauchi K, Yoshida M, Ooya K: Immunohistochemical detection of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in ameloblastomas. J Oral Pathol Med. 2003, 32 (2): 114-120. 10.1034/j.1600-0714.2003.00086.x.CrossRefPubMed
12.
Zhong M, Han YP, Wang J, Li ZJ, Bao G, Yue YL: [Expression of matrix metalloproteinases and tissue inhibitor of metalloproteinase in ameloblastoma]. Shanghai Kou Qiang Yi Xue. 2003, 12 (6): 427-431.PubMed
13.
Pinheiro JJ, Freitas VM, Moretti AI, Jorge AG, Jaeger RG: Local invasiveness of ameloblastoma. Role played by matrix metalloproteinases and proliferative activity. Histopathology. 2004, 45 (1): 65-72. 10.1111/j.1365-2559.2004.01902.x.CrossRefPubMed
14.
Zhong M, Li ZJ, Wang J, Yue YL, Bao G: [The study of the invasive biologic behavior of ameloblastoma]. Zhonghua Kou Qiang Yi Xue Za Zhi. 2004, 39 (1): 45-48.PubMed
15.
Wang X, Fu X, Brown PD, Crimmin MJ, Hoffman RM: Matrix metalloproteinase inhibitor BB-94 (batimastat) inhibits human colon tumor growth and spread in a patient-like orthotopic model in nude mice. Cancer Res. 1994, 54 (17): 4726-4728.PubMed
16.
Watson SA, Morris TM, Parsons SL, Steele RJ, Brown PD: Therapeutic effect of the matrix metalloproteinase inhibitor, batimastat, in a human colorectal cancer ascites model. Br J Cancer. 1996, 74 (9): 1354-1358.CrossRefPubMedPubMedCentral
17.
Rao JS, Bhoopathi P, Chetty C, Gujrati M, Lakka SS: MMP-9 short interfering RNA induced senescence resulting in inhibition of medulloblastoma growth via p16(INK4a) and mitogen-activated protein kinase pathway. Cancer Res. 2007, 67 (10): 4956-4964. 10.1158/0008-5472.CAN-07-0380.CrossRefPubMedPubMedCentral
18.
Kleiner DE, Stetler-Stevenson WG: Quantitative zymography: detection of picogram quantities of gelatinases. Anal Biochem. 1994, 218 (2): 325-329. 10.1006/abio.1994.1186.CrossRefPubMed
19.
Kido A, Krueger S, Haeckel C, Roessner A: Inhibitory effect of antisense aminopeptidase N (APN/CD13) cDNA transfection on the invasive potential of osteosarcoma cells. Clin Exp Metastasis. 2003, 20 (7): 585-592. 10.1023/A:1027383729767.CrossRefPubMed
20.
Hu YB, Li DG, Lu HM: Modified synthetic siRNA targeting tissue inhibitor of metalloproteinase-2 inhibits hepatic fibrogenesis in rats. J Gene MedJ Gene Med. 2007, 9 (3): 217-229. 10.1002/jgm.1009.CrossRef
21.
Bertrand JR, Pottier M, Vekris A, Opolon P, Maksimenko A, Malvy C: Comparison of antisense oligonucleotides and siRNAs in cell culture and in vivo. Biochem Biophys Res Commun. 2002, 296 (4): 1000-1004. 10.1016/S0006-291X(02)02013-2.CrossRefPubMed
22.
Elbashir SM, Harborth J, Weber K, Tuschl T: Analysis of gene function in somatic mammalian cells using small interfering RNAs. Methods. 2002, 26 (2): 199-213. 10.1016/S1046-2023(02)00023-3.CrossRefPubMed
23.
Miyagishi M, Hayashi M, Taira K: Comparison of the suppressive effects of antisense oligonucleotides and siRNAs directed against the same targets in mammalian cells. Antisense Nucleic Acid Drug Dev. 2003, 13 (1): 1-7. 10.1089/108729003764097296.CrossRefPubMed
24.
Yokota T, Miyagishi M, Hino T, Matsumura R, Tasinato A, Urushitani M, Rao RV, Takahashi R, Bredesen DE, Taira K, Mizusawa H: siRNA-based inhibition specific for mutant SOD1 with single nucleotide alternation in familial ALS, compared with ribozyme and DNA enzyme. Biochem Biophys Res Commun. 2004, 314 (1): 283-291. 10.1016/j.bbrc.2003.12.098.CrossRefPubMed
25.
Birkedal-Hansen B, Pavelic ZP, Gluckman JL, Stambrook P, Li YQ, Stetler-Stevenson WG: MMP and TIMP gene expression in head and neck squamous cell carcinomas and adjacent tissues. Oral Dis. 2000, 6 (6): 376-382.CrossRefPubMed
26.
Chetty C, Bhoopathi P, Joseph P, Chittivelu S, Rao JS, Lakka S: Adenovirus-mediated small interfering RNA against matrix metalloproteinase-2 suppresses tumor growth and lung metastasis in mice. Mol Cancer Ther. 2006, 5 (9): 2289-2299. 10.1158/1535-7163.MCT-06-0169.CrossRefPubMed
27.
Chetty C, Bhoopathi P, Lakka SS, Rao JS: MMP-2 siRNA induced Fas/CD95-mediated extrinsic II apoptotic pathway in the A549 lung adenocarcinoma cell line. Oncogene. 2007
28.
Verstappen J, Von den Hoff JW: Tissue inhibitors of metalloproteinases (TIMPs): their biological functions and involvement in oral disease. J Dent Res. 2006, 85 (12): 1074-1084.CrossRefPubMed
29.
Ring P, Johansson K, Hoyhtya M, Rubin K, Lindmark G: Expression of tissue inhibitor of metalloproteinases TIMP-2 in human colorectal cancer--a predictor of tumour stage. Br J Cancer. 1997, 76 (6): 805-811.CrossRefPubMedPubMedCentral
30.
Brummer O, Athar S, Riethdorf L, Loning T, Herbst H: Matrix-metalloproteinases 1, 2, and 3 and their tissue inhibitors 1 and 2 in benign and malignant breast lesions: an in situ hybridization study. Virchows Arch. 1999, 435 (6): 566-573. 10.1007/s004280050442.CrossRefPubMed
31.
Zhang B, Huang HZ, Tao Q, Liu XQ, Wei J: [Association of matrix metalloproteinase-2 activity with cell proliferation and growth in ameloblastoma]. Hua Xi Kou Qiang Yi Xue Za Zhi. 2006, 24 (1): 7-10.PubMed
Metadata
Title
Suppression of local invasion of ameloblastoma by inhibition of matrix metalloproteinase-2 in vitro
Authors
Anxun Wang
Bin Zhang
Hongzhang Huang
Leitao Zhang
Donglin Zeng
Qian Tao
Jianguang Wang
Chaobin Pan
Publication date
01-12-2008
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2008
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/1471-2407-8-182

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