Epigenetic regulation of matrix metalloproteinase expression in ameloblastoma

Farias, Lucyana Conceição; Gomes, Carolina Cavaliéri; Rodrigues, Marcela; Castro, Wagner Henriques; Lacerda, Júlio César Tanos de; Ferreira, Efigênia Ferreira e; Gomez, Ricardo Santiago

doi:10.1186/1472-6890-12-11

Cited by 34 publications

(26 citation statements)

References 31 publications

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“…Estimation of DNA methylation revealed hypomethylation at the promoter regions of MMP2 and MMP9 in placental villi, suggesting a similar role of DNA hypomethylation in activating expression of these invasion-promoting genes in placental tissue, as observed in the cancerous tissue (Shukeir et al 2006, Farias et al 2012. Emerging evidences suggest a significant role of chromatin-remodeling complexes in regulating expression of MMPs (Yan et al 2003, Chang et al 2006.…”

Section: Discussionmentioning

confidence: 99%

Imbalance between matrix metalloproteinases and their tissue inhibitors in preeclampsia and gestational trophoblastic diseases

Rahat¹,

Sharma²,

Bagga³

et al. 2016

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The invasion cascade exhibited by placental trophoblasts and cancerous cells bears many similarities, and it is attributed to extracellular matrix degradation mediated by matrix metalloproteinases (MMPs). Although proper and controlled invasion by trophoblasts into the maternal uterus is an essential requirement for maintenance of normal pregnancy, any abnormality in this phenomenon results in the development of invasion-related disorders such as gestational trophoblastic diseases (GTDs) and preeclampsia. We studied the epigenetic basis of differential expression of two placental MMPs (MMP2 and MMP9) and tissue inhibitors of metalloproteinases (TIMP2 and TIMP1) during normal gestation and invasion-related disorders, i.e., preeclampsia and GTDs. Our study suggests the association of H3K9/27me3 with differential expression of these MMPs and their inhibitors, which regulate the placental invasion during normal pregnancy, whereas no role of CpG methylation was observed in the differential expression of MMPs/TIMPs. Further, development of GTDs was associated with abnormally higher expression of these MMPs and lower levels of their inhibitors, whereas the reverse trends were observed for MMPs and their TIMPs in case of preeclampsia, in association with abnormal changes in H3K9/27me3. These results suggest the involvement of higher levels of MMPs in an aggressive invasive behavior depicted by GTDs, whereas lower levels of these MMPs in shallow and poor invasive phenotype associated with preeclampsia. Thus, our study shows the significance of a proper balance regulated by histone trimethylation between differential expression of MMPs and their TIMPs for maintaining normal pregnancy and its deregulation as a contributing factor for pathogenesis of invasive disorders during pregnancy.

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Section: Discussionmentioning

confidence: 99%

Imbalance between matrix metalloproteinases and their tissue inhibitors in preeclampsia and gestational trophoblastic diseases

Rahat¹,

Sharma²,

Bagga³

et al. 2016

Reproduction

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“…MSP analysis for human MMP-2 was performed as described previously (Chernov et al. 2009; Farias et al 2012) (see Fig. S1A).…”

Section: Methodsmentioning

confidence: 99%

S100A8/A9 regulates MMP-2 expression and invasion and migration by carcinoma cells

Silva

Argyris

Zou

et al. 2014

The International Journal of Biochemistry & Cell Biology

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Intracellular calprotectin (S100A8/A9) functions in the control of the cell cycle checkpoint at G2/M. Dysregulation of S100A8/A9 appears to cause loss of the checkpoint, which frequently characterizes head and neck squamous cell carcinoma (HNSCC). In the present study, we analyzed carcinoma cells for other S100A8/A9-directed changes in malignant phenotype. Using a S100A8/A9-negative human carcinoma cell line (KB), transfection to express S100A8 and S100A9 caused selective down-regulation of MMP-2 and inhibited in vitro invasion and migration. Conversely, silencing of endogenous S100A8 and S100A9 expression in TR146 cells, a well-differentiated HNSCC cell line, increased MMP-2 activity and in vitro invasion and migration. When MMP-2 expression was silenced, cells appeared to assume a less malignant phenotype. To more closely model the architecture of cell growth in vivo, cells were grown in a 3D collagen substrate, which was compared to 2D. Growth on 3D substrates caused greater MMP-2 expression. Whereas hypermethylation of CpG islands occurs frequently in HNSCC, S100A8/A9-dependent regulation of MMP-2 could not be explained by modification of the upstream promoters of MMP2 or TIMP2. Collectively, these results suggest that intracellular S100A8/A9 contributes to the cancer cell phenotype by modulating MMP-2 expression and activity to regulate cell migration and mobility.

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“…In the present study, no difference was observed in the expression of MMP-9 between ameloblastoma and AOT. This result does not reflect the distinct patterns of aggressiveness seen in such tumors, such as suggested by the findings of Farias et al [17] and Henriques et al [18].…”

Section: Discussionmentioning

confidence: 42%

Comparação da imunoexpressão de VEGF, TGF-β e MMP-9 em ameloblastoma e tumor odontogênico adenomatóide

Ferreira

Lima

Maia

et al. 2015

Rev. Odonto Ciênc. (Online)

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Purpose: Studies on odontogenic tumors have identified various molecular dysfunctions involved on their development, and some mechanisms such as angiogenesis and matrix modulation, are useful means of investigating the differences in biologic behavior of these tumors. Some important markers to identify tumor aggressiveness by immunohistochemistry are VEGF, TGF-β and MMP-9 proteins. This study aimed to compare the immunohistochemical expression of VEGF, TGF-β, and MMP-9 in ameloblastoma and adenomatoid odontogenic tumor (AOT). Methods: Immunoexpression of VEGF, TGF-β, and MMP-9 was studied in 15 solid ameloblastomas, and 15 AOTs. A semi-quantitative analysis of the immunostained cells was performed, and the statistical analysis was made using the Mann-Whitney nonparametric and Spearman correlation test, with significance level at .05 (P<.05). Results: A higher epithelial immunoexpression of VEGF and TGF-β was observed in ameloblastoma and AOT, respectively, and the stromal reactivity to VEGF was statistically higher in ameloblastoma (P<.05). No statistical difference was observed for MMP-9 (P>.05). Conclusion:The results suggest the involvement of angiogenesis in tumor progression of ameloblastomas, and the inductive effect of stromal cells in AOT, hence justifying its lower growth potential.

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Epigenetic regulation of matrix metalloproteinase expression in ameloblastoma

Cited by 34 publications

References 31 publications

Imbalance between matrix metalloproteinases and their tissue inhibitors in preeclampsia and gestational trophoblastic diseases

Imbalance between matrix metalloproteinases and their tissue inhibitors in preeclampsia and gestational trophoblastic diseases

S100A8/A9 regulates MMP-2 expression and invasion and migration by carcinoma cells

Comparação da imunoexpressão de VEGF, TGF-β e MMP-9 em ameloblastoma e tumor odontogênico adenomatóide

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