Objective
The objective of this preliminary study was to evaluate the expression of matrix metalloproteinases
(MMPs), tissue inhibitors of metalloproteinases (TIMPs) and growth factors in keratocystic
odontogenic tumors (KOTs).
Study Design
The expression of MMPs, TIMPs, growth factors, and the extracellular signal–regulated
kinase (ERK) 1/2 signaling pathway were assessed by immunohistochemistry in 15 cases
of KOT and 4 cases of calcifying cystic odontogenic tumor (CCOT).
Results
KOT samples expressed significantly higher amounts of MMPs, TIMPs, growth factors,
epidermal growth factor receptor (EGFR), and ERK compared with CCOT samples, with
the exception of MMP-2 and TIMP-1.
Conclusions
MMP-9, TIMP-2, EGF and transforming growth factor α act together and likely regulate
the proliferation and aggressiveness of KOT. ERK-1/2 serves as the transducer of signals
generated by these proteins, which signal through the common receptor, EGFR. This
process may be related to the increased proliferation and aggressiveness observed
in KOT.
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to Oral Surgery, Oral Medicine, Oral Pathology and Oral RadiologyAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Keratocystic odontogenic tumor.in: Barnes L. Eveson J. Reichart P. Sidransky D. World Health Organization classification of tumors Pathology and genetics of head and neck tumors. IARC, Lyon2005: 306-307
- The aggressive nature of the odontogenic keratocyst: is it a benign cystic neoplasm?.Oral Oncol. 2002; 38: 219-226
- Characterization and management of the keratocystic odontogenic tumor in relation to its histopathological and biological features.Oral Oncol. 2010; 46: 219-225
- A systematic review of the recurrence rate for keratocystic odontogenic tumour in relation to treatment modalities.Int J Oral Maxillofac Surg. 2012; 41: 756-767
- Cysts of the oral and maxillofacial regions.3rd ed. Wright, Butterworth-Heinemann, Oxford1992
- Immunohistochemical comparative study of the odontogenic keratocysts and other odontogenic lesions.Med Oral Patol Oral Cir Bucal. 2010; 15: e709-e715
- Om keratocystedr (kolesteratomer) and kaeberne.Tandlaegebladet. 1956; 60: 963-971
- Origin and growth of cysts of the jaws.Ann R Coll Surg Engl. 1967; 40: 306-336
- Extracellular matrix: a matter of life and death.Connect Tissue Res. 2008; 49: 203-206
- Establishment and biological behaviour of human ameloblastoma xenograft in nude mice China.J Oral Maxillofac Surg. 2004; 2: 270-273
- Matrix metalloproteinases involvement in pathologic conditions.Rom J Morphol Embryol. 2010; 51: 215-228
- Matrix metalloproteinases: roles in cancer and metastasis.Front Biosci. 2006; 11: 479-491
- Matrix metalloproteinases stimulate epithelial-mesenchymal transition during tumor development.Clin Exp Metastasis. 2008; 25: 593-600
- Matrix metalloproteinases at cancer tumor–host interface.Semin Cell Dev Biol. 2008; 19: 52-60
- Activation and silencing of matrix metalloproteinases.Semin Cell Dev Biol. 2008; 19: 2-13
- Matrix metalloproteinases: regulators of the tumor microenvironment.Cell. 2010; 141: 52-67
- Clinical significance of MMP-2 and MMP-9 in patients with oral cancer.Head Neck. 2007; 29: 564-572
- Matrix metalloproteinases, TIMPs and growth factors regulating ameloblastoma behaviour.Histopathology. 2010; 57: 128-137
- Keratocystic odontogenic tumor (odontogenic keratocyst): preliminary retrospective review of epidemiologic, clinical, and radiologic features of 261 lesions from university of Turin.J Oral Maxillofac Surg. 2010; 68: 2994-2999
- MMP-13 expression in keratocyst odontogenic tumor associated with NBCCS and sporadic keratocysts.Oral Dis. 2010; 16: 795-800
- Expression of extracellular matrix metalloproteinase inducer in odontogenic cysts.Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2008; 106: 258-263
- Immunohistochemical expression of MMPs 1, 7, and 26 in syndrome and nonsyndrome odontogenic keratocysts.Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2008; 106: 99-105
- Comparative analysis of the immunohistochemical expression of collagen IV, MMP-9, and TIMP-2 in odontogenic cysts and tumors.Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2011; 112: 468-475
- Local invasiveness of ameloblastoma.Histopathology. 2004; 45: 65-72
- Odontogenic tumours.in: Barnes L. Eveson J. Reichart P. Sidransky D. World Health Organization classification of tumours Pathology and genetics of tumours of the head and neck. IARC, Lyon2005: 313
- Immunohistochemical expression of matrix metalloproteinases 1, 2; 7, 9, and 26 in the calcifying cystic odontogenic tumor.Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2011; 112: 609-615
- Epidermal growth factor.J Biol Chem. 1990; 265: 7709-7712
- Matrix metalloproteinases: a review.Crit Rev Oral Biol Med. 1993; 4: 197-250
- The aggressive nature of the odontogenic keratocyst: is it a benign cystic neoplasm?.Oral Oncol. 2002; 38: 407-415
- Role of matrix metalloproteinases in the etiopathogeny of odontogenic cysts.J Bras Patol Med Lab. 2007; 43: 203-209
- Expression of metallothionein in ameloblastoma.J Oral Pathol Med. 2011; 40: 516-519
- Immunohistochemical expression of nuclear factor κB, matrix metalloproteinase 9, and endoglin (CD105) in odontogenic keratocysts, dentigerous cysts, and radicular cysts.Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2011; 112: 476-483
- Interleukin-1alpha–dependent regulation of matrix metalloproteinase-9 (MMP-9) secretion and activation in the epithelial cells of odontogenic jaw cysts.J Dent Res. 2000; 79: 423-430
- A scrutiny of matrix metalloproteinases in osteoclasts: evidence for heterogeneity and for the presence of MMPs synthesized by other cells.Bone. 2004; 35: 1107-1119
- Regulation of matrix metalloproteinase activity in health and disease.FEBS J. 2011; 278: 28-45
- Nuclear localization of matrix metalloproteinases.Prog Histochem Cytochem. 2012; 47: 27-58
- Matrix metalloproteinase-9 and cell division in neuroblastoma cells and bone marrow macrophages.Am J Pathol. 2010; 177: 2870-2885
- The aggressive nature of the odontogenic keratocyst: is it a benign cystic neoplasm?.Oral Oncol. 2002; 38: 323-331
- Biological pathways involved in the aggressive behavior of the keratocystic odontogenic tumor and possible implications for molecular oriented treatment—an overview.Oral Oncol. 2010; 46: 19-24
- A comparative immunohistochemical analysis of COX-2, p53, and Ki-67 expression in keratocystic odontogenic tumors.Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2011; 111: 333-339
- Expressions of Bax, Bcl-2 and Ki-67 in odontogenic keratocysts (keratocystic odontogenic tumor) in comparison with ameloblastomas and radicular cysts.Turk Patoloji Derg. 2012; 28: 49-55
- Immunohistochemical comparison of the expression of p53 and MDM2 proteins in ameloblastomas and keratocystic odontogenic tumors.J Craniofac Surg. 2011; 22: 1652-1656
- Expression of proliferating cell nuclear antigen in ameloblastomas and odontogenic cysts.Oral Oncol. 1998; 34: 408-412
- MAP kinase signalling pathways in cancer.Oncogene. 2007; 26: 3279-3290
- The epidermal growth factor receptor (EGFR) in head and neck cancer: its role and treatment implications.Radiol Oncol. 2006; 1: 11
- Expression of epidermal growth factor (EGF)/transforming growth factor-alpha by human lung cancer cells determines their response to EGF receptor tyrosine kinase inhibition in the lungs of mice.Mol Cancer Ther. 2007; 6: 2652-2663
- Extracellular-regulated kinase–mitogen-activated protein kinase cascade: unsolved issues.J Cell Biochem. 2010; 109: 850-857
- Suppression of EGF-induced tumor cell migration and matrix metalloproteinase-9 expression by capsaicin via the inhibition of EGFR-mediated FAK/Akt, PKC/Raf/ERK, p38 MAPK, and AP-1 signalling.Mol Nutr Food Res. 2011; 55: 594-605
- Activated extracellular signal-regulated kinase is an independent prognostic factor in clinically confined renal cell carcinoma.Cancer. 2009; 115: 3457-3467
- Invadopodia proteins, cortactin and membrane type I matrix metalloproteinase (MT1-MMP) are expressed in ameloblastoma.Histopathology. 2011; 59: 1266-1269
- Specialized tumor cells structures for the focal degradation of the extracellular matrix.Cancer Metastasis Rev. 2009; 28: 137-149
- Molecular signature of MT1-MMP: transactivation of the downstream universal gene network in cancer.Cancer Res. 2008; 68: 4086-4096
Article info
Publication history
Accepted:
June 16,
2012
Received in revised form:
June 15,
2012
Received:
February 10,
2012
Identification
Copyright
© 2012 Elsevier Inc. Published by Elsevier Inc. All rights reserved.