Expression and prognostic role of MMP2, MMP9, MMP13, and MMP14 matrix metalloproteinases in sinonasal and oral malignant melanomas

Kondratiev, Svetlana; Gnepp, Douglas R.; Yakirevich, Evgeny; Sabo, Edmond; Annino, Donald J.; Rebeiz, Elie E.; Laver, Nora

doi:10.1016/j.humpath.2007.07.003

Cited by 47 publications

(32 citation statements)

References 27 publications

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“…It is of note that the activity of MMP-9 is modulated at three levels, namely, gene expression, proenzyme activation, and inhibition of the hydrolytic ability by specific inhibitors (34)(35)(36). MMP-9 expression has been found to be activated or enhanced by oncogenic proteins and elevated in many cancer types, including breast cancer, prostate cancer, melanoma, bladder cancer, pancreatic cancer, and gliomas, and to correlate with the prognosis of cancer patients (37)(38)(39)(40)(41)(42). In addition to its effect on the invasive ability of tumor cells, MMP-9 also plays roles in tumor angiogenesis and is involved in a variety of signaling cascades leading to cancer progression (43,44).…”

Section: Discussionmentioning

confidence: 99%

Astrocyte Elevated Gene-1 Upregulates Matrix Metalloproteinase-9 and Induces Human Glioma Invasion

et al. 2010

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The poor prognosis of malignant gliomas is largely attributed to their highly invasive nature. The molecular mechanism underlying the invasiveness of glioma cells, however, remains to be elucidated. The present study found that astrocyte elevated gene-1 (AEG-1) was upregulated in human glioma cell lines and glioma tissues compared with normal astrocytes and brain tissues. AEG-1 was found to be upregulated in 265 of 296 (89.5%) glioma sections, and the AEG-1 expression level significantly correlated with clinicopathologic stages of gliomas. Ectopic expression or short hairpin RNA silencing of AEG-1 significantly enhanced or inhibited, respectively, the invasive ability of glioma cells. At the molecular level, we showed that upregulated AEG-1 in glioma cells interacted with matrix metalloproteinase-9 (MMP-9) promoter and transactivated MMP-9 expression, whereas knockdown of AEG-1 expression reduced the level of MMP-9. Two regions in MMP-9 promoter were found to be involved in the interaction with AEG-1. Suppression of endogenous MMP-9 abrogated the effects of AEG-1 on invasiveness. Consistent with these observations, immunostaining analysis revealed a significant correlation between the expressions of AEG-1 and MMP-9 in a cohort of clinical glioma samples. Moreover, intracranial xenografts of glioma cells engineered to express AEG-1 were highly invasive compared with the parental cells and expressed high level of MMP-9. Collectively, these findings provide evidence that AEG-1 contributes to glioma progression by enhancing MMP-9 transcription and, hence, tumor cell invasiveness, and underscore the importance of AEG-1 in glioma development and progression. Cancer Res; 70(9); 3750-9. ©2010 AACR.

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Section: Discussionmentioning

confidence: 99%

Astrocyte Elevated Gene-1 Upregulates Matrix Metalloproteinase-9 and Induces Human Glioma Invasion

et al. 2010

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“…MMP9, also known as gelatinase B, has been associated with tumor progression in multiple studies (31,(34)(35)(36)(37). In particular, several analyses show that expression of MMP9 is a prognostic indicator in breast cancer patients (36,38,39).…”

Section: Discussionmentioning

confidence: 99%

Clinical Implications of the Influence of Ehm2 on the Aggressiveness of Breast Cancer Cells through Regulation of Matrix Metalloproteinase-9 Expression

Ye²,

Mansel³

et al. 2010

Molecular Cancer Research

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Ehm2, a member of NF2/ERM/4.1 superfamily, has been indicated in disease progression and metastasis of prostate cancer. However, its function and implication in malignancies remain largely unknown. The present study aimed to examine the role of Ehm2 in breast cancer. We first constructed a hammerhead ribozyme transgene to knock down Ehm2 expression in breast cancer cells. The effect on growth, cell matrix adhesion, motility, and invasion following knockdown of Ehm2 was then investigated using in vitro models. Reduction of Ehm2 had inhibitory effects on in vitro growth and invasion of breast cancer cells. Flow cytometric analysis showed that knockdown of Ehm2 induced apoptosis. Knockdown of Ehm2 also significantly decreased matrix metalloproteinase 9 mRNA and protein levels, as well as the corresponding enzymatic activity, and consequently led to a reduction of the invasion. The expression pattern of Ehm2 in a cohort of breast specimens (normal, n = 33; cancer, n = 127) was analyzed using both quantitative real-time PCR and immunohistochemical staining. Increased expression of Ehm2 in breast cancer was seen at both mRNA and protein levels. Higher levels of Ehm2 transcripts were correlated with disease progression, metastasis, and poor prognosis. Disease-free survival of the patients with lower levels of Ehm2 was 135.8 (95% confidence interval, 125.1-146.5) months, significantly longer compared with 102.5 (95% confidence interval, 78.7-126.4) months of patients with higher levels of Ehm2 expression (P = 0.039). Taken together, increased Ehm2 expression correlates with poor prognosis and metastasis. Ehm2 may promote the invasive ability of breast cancer cells via regulation of matrix metalloproteinase 9. Mol Cancer Res; 8(11); 1501-12.

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“…After reviewing the full text of the remaining 21 studies, we ultimately included 11 studies [11][12][13][14][15][16][17][18][19][20][21] in the final analysis. Ten studies were excluded from the final review for these reasons: (1) insufficient survival data (n=8) [23][24][25][26][27][28][29][30] and (2) MT1-MMP expression was not measured by immunohistochemistry (n =2) [31,32]. Figure 1 shows a flow diagram with the numbers of relevant studies.…”

Section: Eligible Studiesmentioning

confidence: 99%

MT1-MMP is not a good prognosticator of cancer survival: evidence from 11 studies

Lin

et al. 2014

Tumor Biol.

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MT1-MMP exhibits diverse expressions in patients with cancer and could be considered as potential prognostic biomarker of cancer. We performed a meta-analysis aiming to provide more sufficient evidence that MT1-MMP expression is associated with poor overall survival in several types of cancers. We systematically searched the studies from databases and carefully identified based on eligibility criteria. The association between MT1-MMP expression and overall survival in cancers was estimated using Review Manager. A total of 11 literatures which included 1,918 cancer patients were combined in the final analysis. Meta-analysis revealed that MT1-MMP overexpression was associated with an unfavorable overall survival and the pooled hazard ratio (HR) and corresponding 95 % confidence interval (CI) was 2.46 (95 % CI 1.75-3.47). From subgroup analyses, we identified that MT1-MMP was an independent prognostic factor for lung cancer and gastric cancer, and HRs (95 % CI) were 3.73 (95 % CI 2.67-5.21) and 2.46 (95 % CI 1.69-3.59), respectively. In conclusion, MT1-MMP is a potential prognostic factor in human cancers.

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Expression and prognostic role of MMP2, MMP9, MMP13, and MMP14 matrix metalloproteinases in sinonasal and oral malignant melanomas

Cited by 47 publications

References 27 publications

Astrocyte Elevated Gene-1 Upregulates Matrix Metalloproteinase-9 and Induces Human Glioma Invasion

Astrocyte Elevated Gene-1 Upregulates Matrix Metalloproteinase-9 and Induces Human Glioma Invasion

Clinical Implications of the Influence of Ehm2 on the Aggressiveness of Breast Cancer Cells through Regulation of Matrix Metalloproteinase-9 Expression

MT1-MMP is not a good prognosticator of cancer survival: evidence from 11 studies

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