Immunohistochemical detection of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in ameloblastomas

Kumamoto, Hiroyuki; Yamauchi, Kensuke; Yoshida, Mitsuhide; Ooya, Kiyoshi

doi:10.1034/j.1600-0714.2003.00086.x

Cited by 68 publications

(107 citation statements)

References 27 publications

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“…Similarly to the present study, Silveira et al 8 observed more pronounced expression of MMP-9 in the mesenchymal component of KOTs compared with RCs and DCs, a finding supporting the hypothesis of a more aggressive behavior of this tumor compared with other cysts. In the study by Kumamoto et al, 15 immunoreactivity to MMP-9 was stronger in the stroma of ameloblastomas than in the mesenchymal component of tooth germs, suggesting that an increased production of this protein by neoplastic cells is related to the transformation of odontogenic tissues and aggressiveness of this tumor. Ribeiro et al 29 also found intense immunostaining for this gelatinase in the parenchyma and stroma of ameloblastomas, indicating its possible participation in the growth of these tumors.…”

Section: Discussionmentioning

confidence: 89%

“…6 Several factors have been associated with the aggressive behavior of ameloblastomas, such as an increased proliferation potential, 12 alterations in the expression of tumor suppressor genes, and the aberrant expression of cell cycle-regulating proteins, 13 adhesion molecules, 14 and MMPs and their inhibitors (TIMPs). 15 In addition, Silveira et al 8 suggested that the mechanism of expansion of KOTs, DCs, and RCs may also be influenced, or even be conducted, by the secretion of MMPs. Thus, an exuberant expression of MMPs might be related to a higher aggressiveness of cystic lesions.…”

Section: Discussionmentioning

confidence: 99%

“…16 On the basis of these observations it could be suggested that the degradation of ECM is not dependent on the expression of a single MMP, but rather that the combined action of several MMPs and TIMPs is essential for the efficient degradation of the BM and interstitial stroma. Kumamoto et al 15 performed an immunohistochemical study and found that increased expression of TIMP-1 and TIMP-2 was related to weak immunoreactivity for MMP-9. According to those authors, it is possible that the TIMPs contribute to suppress tumor progression in ameloblastomas through the inhibition of MMP-9 activity.…”

Section: Discussionmentioning

confidence: 99%

“…15 Expression of gelatinases/type IV collagenases has been investigated in numerous tumors and has been shown to be associated with an invasive phenotype and metastatic potential of tumor cells. 24,25 Preclinical trials have shown that squamous cell carcinomas express high levels of MMPs in vivo and that the inhibition of these enzymes in vitro and in animal models reduces the invasion potential and metastatic capacity of the tumor.…”

Section: Discussionmentioning

confidence: 99%

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Comparative analysis of the immunohistochemical expression of collagen IV, MMP-9, and TIMP-2 in odontogenic cysts and tumors

Henriques

Vasconcelos

Galvão

et al. 2011

Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, an

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Objective. The aim of this study was to evaluate the immunohistochemical expression of collagen IV, matrix metalloproteinase (MMP) 9 and tissue inhibitor of MMP (TIMP) 2 in dentigerous cysts (DCs), radicular cysts (RCs), keratocystic odontogenic tumors (KOTs), and ameloblastomas. Study design. Twenty cases of DCs, 20 RCs, 20 KOTs, and 20 ameloblastomas were selected and analyzed by immunohistochemistry. Results. Most DCs and RCs showed continuous and Ͼ50% staining for collagen IV in the basement membrane of the epithelium, whereas predominantly discontinuous thin and Յ50% staining was observed in KOTs and ameloblastomas, with a significant difference in staining percentage (P Ͻ .001). MMP-9 was diffusely distributed and localized in both epithelial and mesenchymal cells of all of the lesions analyzed. The staining percentage was higher in the epithelium (P ϭ .058) and mesenchyme (P ϭ .005) of KOTs and ameloblastomas. Moreover, the distribution pattern, location, and percentage of expression of TIMP-2 were similar in the lesions studied, except for ameloblastoma, with a significant difference in staining percentage (P Ͻ .001).Conclusion. These results demonstrate that the interaction between collagen IV, MMP-9, and TIMP-2 is an important factor for the establishment of differences in the biologic behavior of the odontogenic cysts and tumors studied. Factors related to the epithelial and mesenchymal components participate in the regulation of the growth of odontogenic cystic lesions and tumors. 1 The altered expression of specific proteins of the extracellular matrix (ECM), associated with the exuberant presence of matrix metalloproteinases (MMPs) and the absence of expression of metalloproteinase inhibitors (TIMPs), may influence the behavior of these lesions. In the case of tumors, this situation contributes to the growth and higher aggressiveness of the tumor. 2 The odontogenic keratocyst, recently reclassified as keratocystic odontogenic tumor (KOT), 3 is known for its aggressive nature and high rate of recurrence, especially compared with other odontogenic cysts. 4 Ameloblastoma is a locally aggressive benign epithelial odontogenic tumor with a marked invasion potential that results in multiple recurrences after enucleation and curettage. 5 In contrast, dentigerous (DC) and radicular (RC) cysts show an indolent behavior and rarely recur after surgical removal. KOT presents a cystic structure similar to that of DC and RC, but its invasive and destructive growth is similar to that of ameloblastoma. 6 KOT, ameloblastoma, DC, and RC show distinct evolutions and biologic behaviors. In view of this fact, a growing number of studies have tried to identify

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Section: Discussionmentioning

confidence: 89%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Comparative analysis of the immunohistochemical expression of collagen IV, MMP-9, and TIMP-2 in odontogenic cysts and tumors

Henriques

Vasconcelos

Galvão

et al. 2011

Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, an

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“…[13][14][15] MMP-1 (collagenase-1, interstitial collagenase), synthesized by a wide variety of normal cells, such as fibroblasts, macrophages, and endothelial and epithelial cells, is one of the major proteases that can degrade the triple-helical domain of type I fibrillar collagen. [16][17][18] Type I collagen, responsible for connective tissue strength and rigidity, is the main component of the organic bone matrix. 19 A possible role for MMP-1 in keratinocyte migration 18 has been reported and the overexpression of this protease can be observed in advanced epithelial malignant tumors.…”

mentioning

confidence: 99%

Immunohistochemical expression of MMPs 1, 7, and 26 in syndrome and nonsyndrome odontogenic keratocysts

Cavalcante

Pereira

Nonaka

et al. 2008

Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, an

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Objective. The objective of this study was to analyze the expression of matrix metalloproteinases (MMPs) 1, 7, and 26 in odontogenic keratocysts (OKCs) associated with Gorlin syndrome (SOKCs) and nonsyndrome OKCs (NSOKCs). Study design. Twenty-one SOKCs and 20 NSOKCs were evaluated for epithelial expression of MMP-1, MMP-7, and MMP-26 and for mesenchymal expression of MMP-1 by immunohistochemistry. Results. Strong epithelial positivity to MMP-1 was observed in 76% of SOKCs and in 15% of NSOKCs (P Ͻ .05). Strong mesenchymal immunoreactivity to MMP-1 was observed in 38% of SOKCs and in 20% of NSOKCs (P Ͼ .05). Epithelial immunoreactivity to MMP-7 was strongly positive in 67% of SOKCs and in 40% of NSOKCs (P Ͼ .05). For MMP-26, strong positivity was found in 62% of SOKCs, in contrast to 35% of NSOKCs (P Ͼ .05). Conclusion. MMPs-1, Ϫ7 and Ϫ26 may play important roles in the biology of OKCs. Furthermore, the presence of these proteases at higher levels in SOKCs may help to explain increased OKC aggressiveness associated with nevoid basal cell carcinoma syndrome.

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MMP‐7, ‐8, ‐9, E‐cadherin, and beta‐catenin expression in 34 ameloblastoma cases

Kelppe

Thorén

Haglund

et al. 2020

Clinical & Exp Dental Res

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Objectives Ameloblastoma is a benign, locally aggressive odontogenic tumor with high recurrence rates. Matrix metalloproteinases (MMPs) mediate extracellular integrity in normal and pathological conditions, and exert multiple functions coordinating inflammation and tumor progression. E‐cadherin and beta‐catenin are adherence junction molecules in cell‐to‐cell connections. We investigated the involvement of MMP‐7, ‐8, ‐9, E‐cadherin, and beta‐catenin in ameloblastoma and the surrounding extracellular matrix. Material and methods Our material consisted of 30–34 tissue samples from ameloblastoma patients of Helsinki University Hospital. We used immunohistochemistry to detect the expression of the biomarkers. Two oral pathologists independently scored the immunoexpression intensities and statistical calculations were made based on the results. Results E‐cadherin expression was weaker in the maxillary than in mandibular ameloblastomas. Beta‐catenin was expressed in the ameloblastoma cell membranes. We detected MMP‐8 and ‐9 expression in polymorphonuclear neutrophils in the extracellular area and these MMPs correlated positively with each other. Osteoclasts lining bone margins and multinuclear giant cells expressed MMP‐9. Neither MMP‐8 nor MMP‐9 immunoexpression could be detected in ameloblastoma cells. MMP‐7 expression was seen in some apoptotic cells. Conclusion The fact that E‐cadherin immunoexpression was weaker in maxillary compared to mandibular ameloblastomas might associate to earlier recurrences. It promotes the idea of mandibular and maxillary ameloblastoma exerting differences in their biologies. We detected MMP‐8 and ‐9 in polymorphonuclear neutrophils which relates to these MMPs participating in extracellular remodeling through a mild inflammatory process. Bone degradation around ameloblastoma may be due to MMP‐9 in osteoclasts but this phenomenon might be an independent process and needs further investigations.

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Immunohistochemical detection of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in ameloblastomas

Cited by 68 publications

References 27 publications

Comparative analysis of the immunohistochemical expression of collagen IV, MMP-9, and TIMP-2 in odontogenic cysts and tumors

Comparative analysis of the immunohistochemical expression of collagen IV, MMP-9, and TIMP-2 in odontogenic cysts and tumors

Immunohistochemical expression of MMPs 1, 7, and 26 in syndrome and nonsyndrome odontogenic keratocysts

MMP‐7, ‐8, ‐9, E‐cadherin, and beta‐catenin expression in 34 ameloblastoma cases

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