Local invasiveness of ameloblastoma. Role played by matrix metalloproteinases and proliferative activity

Pinheiro, João de Jesus Viana; Freitas, Vanessa M.; Moretti, Ana Iochabel Soares; Jorge, A. G.; Jaeger, Ruy Gastaldoni

doi:10.1111/j.1365-2559.2004.01902.x

Cited by 104 publications

(143 citation statements)

References 23 publications

Supporting

Mentioning

112

Contrasting

Unclassified

Order By: Relevance

“…of cases suggest that MMP-1 production by these cells might be associated with tumor cell progression of ameloblastomas. Based on the findings reported by Kumamoto et al 16 and Pinheiro et al, 21 it could be suggested that the MMP-1 expression by OKCs cells observed in our study might be related to a functional role for this protease beyond simple extracellular matrix degradation. In fact, MMP-1 activity is capable of releasing growth factors and cytokines present in the surrounding organic bone matrix.…”

Section: Table II Immunoreactivity To Matrix Metalloproteinases In Osupporting

confidence: 79%

“…Moreover, the highest epithelial immunoreactivity to MMP-1 in SOKCs (P Ͻ .05) may help to explain the increased aggressiveness of this lesion, when associated with nevoid basal cell carcinoma syndrome, reported in the literature. 8,10,12 The synthesis and secretion of the proenzyme form of MMP-1 by cultured fibroblasts from OKCs 34 and reports implying a role for MMP-1 in tumor progression 16 and local invasiveness of ameloblastomas, 21 as well as in keratinocyte migration, 18 invasion, and metastasis 20 reinforce the importance of this protease in the OKC biology.…”

Section: Discussionmentioning

confidence: 90%

“…Therefore, additional studies are needed to clarify a possible diagnostic utility for MMP-1 epithelial immunoreactivity in OKCs. Pinheiro et al, 21 using immunohistochemical, zymographic, and western blot analysis, showed that parenchymal and stromal cells of ameloblastoma can produce MMPs-1, Ϫ2, and Ϫ9. In addition, these authors found increased proliferation indexes of ameloblastoma cells in close proximity to bone, assessed by the Ag-NOR technique, suggesting an interdependent mechanism involving the action of MMPs and the proliferative activity of ameloblastomas.…”

Section: Discussionmentioning

confidence: 99%

“…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. 20 Furthermore, MMP-1 has been implicated in tumor progression 16 and local invasiveness 21 of ameloblastomas.…”

mentioning

confidence: 99%

See 3 more Smart Citations

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

View full text Add to dashboard Cite

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.

show abstract

Section: Table II Immunoreactivity To Matrix Metalloproteinases In Osupporting

confidence: 79%

Section: Discussionmentioning

confidence: 90%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

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

View full text Add to dashboard Cite

show abstract

“…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.…”

mentioning

confidence: 99%

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

View full text Add to dashboard Cite

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

show abstract

Fibroblasts promote the collective invasion of ameloblastoma tumor cells in a 3D coculture model

et al. 2017

View full text Add to dashboard Cite

Ameloblastoma is a benign tumor of the odontogenic epithelium with several histological subtypes. All subtypes of ameloblastoma contain abundant stroma; the tumor cells invade collectively into the surrounding tissues without losing intratumor cell attachments. However, the molecular mechanisms mediating ameloblastoma invasion remain unclear. Here, we evaluated the functional significance of the interactions between ameloblastoma tumor cells and stromal fibroblasts on collective cellular invasion using a three‐dimensional cultivation method, double‐layered collagen gel hemisphere ( DL ‐ CGH ) culture. The AM ‐1 plexiform and AM ‐3 follicular human ameloblastoma cell lines and HFF ‐2 human fibroblasts were labeled with GFP and DsRed, respectively. Collective cellular invasion of ameloblastoma cells was assessed in the presence or absence of fibroblasts. Notably, without fibroblasts, AM ‐1 cells formed sharp, plexiform‐like invasive processes, whereas AM ‐3 cells formed a series of blunt processes often observed during collective migration. In comparison, under the cocultures with HFF ‐2 fibroblasts, AM ‐3 cells formed tuft‐like invasive processes and collectively invaded into outer layer more than that observed with AM ‐1 cells. Moreover, HFF ‐2 fibroblasts localized to the tips of the invasive tumor processes. These findings suggest that tumor‐associated cells assist tumor cell invasion. Microscopic analysis of sectioned three‐dimensional cultures revealed that AM ‐3/ HFF ‐2 hemispheres were histologically similar to follicular ameloblastoma tumor samples. Therefore, our findings suggest that ameloblastoma subtypes exhibit distinct invasion patterns and that fibroblasts promote collective tumor invasion in follicular ameloblastoma.

show abstract

Local invasiveness of ameloblastoma. Role played by matrix metalloproteinases and proliferative activity

Abstract: Our results suggest an interdependent mechanism involving MMPs and proliferation of ameloblastoma cells, which may contribute to the local invasiveness of this tumour.

Cited by 104 publications

References 23 publications

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

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

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

Fibroblasts promote the collective invasion of ameloblastoma tumor cells in a 3D coculture model

Contact Info

Product

Resources

About