Clinical significance of MMP‐2 and MMP‐9 in patients with oral cancer

Patel, Beena P.; Shah, Sonal Patel; Shukla, Shilin N.; Shah, Pankaj; Patel, Prabhudas S.

doi:10.1002/hed.20561

Cited by 120 publications

(107 citation statements)

References 28 publications

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“…Our data suggest that one mechanism by which FLJ10540 may promote tumor cell migration and invasion is through the increased expression and proteolytic activity of MMP-2, which specifically degrades the basement membrane (Figure 7a). The MMP-2 has been suggested to play critical roles in oral cancer migration and metastasis (Munshi et al, 2002;Ruokolainen et al, 2006;Patel et al, 2007), and the upregulation of MMP-2 has been associated with a poor prognosis in oral cancer patients (Ruokolainen et al, 2006). The activation of proMMP-2 has been considered to be a particularly important step in tumor invasion (Itoh et al, 2001).…”

Section: Discussionmentioning

confidence: 99%

“…MMP-2 is also closely associated with tumor progression and metastasis in human OCSCC; specifically, they have been shown to be localized to the advancing tumor front and are implicated in metastatic dissemination (Hong et al, 2000). The elevated expression of the MMP-2 immunoreactive protein is correlated with a poor prognosis in OCSCC (Ruokolainen et al, 2004;Gao et al, 2005;Patel et al, 2007). In addition, MMP-2 expression could be regulated by several transcription factors, including YB-1 (Mertens et al, 1997), Sp1 (Qin et al, 1999), p53 (Bian and Sun, 1997), Stat3 (Xie et al, 2004) and FOXM1 (Dai et al, 2007); however, the molecular mechanisms by which MMP-2 is activated and controls tumor metastasis in OCSCC remain elusive.…”

Section: Introductionmentioning

confidence: 99%

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Expression of FLJ10540 is correlated with aggressiveness of oral cavity squamous cell carcinoma by stimulating cell migration and invasion through increased FOXM1 and MMP-2 activity

Chien

et al. 2009

Oncogene

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Matrix metalloproteinase (MMP)-2 plays critical roles in tumor development and in the metastasis of multiple cancers, including human oral cavity squamous cell carcinoma (OCSCC). One of the upstream regulators of MMP-2 is FOXM1, which is overexpressed in a microarray dataset of OCSCC. It is interesting that FLJ10540 exhibits similar gene expression profiles with MMP-2 and FOXM1, raising the possibility that these molecules might participate in MMP-2-elicited cancer progression and metastasis of OCSCC. To examine this connection, we first showed that FLJ10540 was significantly overexpressed in OCSCC. A strong FLJ10540 expression was significantly correlated with an advanced tumor node metastasis stage and the cumulative 5-year survival rate. Thus, an elevated FLJ10540 expression is an indicator of poor survival. Functionally, FLJ10540 had the abilities to stimulate cell migration and invasion in oral cancer cells through increased FOXM1 and MMP-2 expressions. Conversely, the depletion of the FLJ10540 expression by small interefering RNAs suppressed the FOXM1 and MMP-2 protein expressions. The suppression of either FLJ10540 or FOXM1 could cause significant inhibition on cell migratory and invasive ability in oral cancer cells. Finally, the immunohistochemical and western blotting analyses of human aggressive OCSCC specimens showed a significant positive correlation among FLJ10540, FOXM1 and MMP-2 expressions. These findings suggest that FLJ10540 is not only an important prognostic factor but also a new therapeutic target in the FLJ10540/FOXM1/MMP-2 pathway for OCSCC treatment.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Expression of FLJ10540 is correlated with aggressiveness of oral cavity squamous cell carcinoma by stimulating cell migration and invasion through increased FOXM1 and MMP-2 activity

Chien

et al. 2009

Oncogene

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“…The cleavage of laminin-5 by MMP-2 and MMP-14 reveals its matricryptic site (hidden forms of extracellular matrix molecules that can be exposed by structural modifications), favoring cell motility. 22 Patel et al 23 evaluated the expression of MMP-2 and 9 and the plasma concentration of these gelatinases in tissue samples with malignant lesions. The authors suggested that the expression of these MMPs could be a useful diagnostic marker in the detection and monitoring of malignant lesions, given that tissue expression of these enzymes was shown to be high in these lesions and in the plasma.…”

Section: Zinc and Metalloproteinases Of The Extracellular Matrixmentioning

confidence: 99%

Zinc and metalloproteinases 2 and 9: What is their relation with breast cancer?

Holanda

Oliveira²,

Cruz³

et al. 2017

Rev. Assoc. Med. Bras.

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Zinc is the catalytic component of proteins that regulate responses to DNA damage, intracellular signaling enzymes, and matrix metalloproteinases, which are important proteins in carcinogenesis. The objective of this review is to bring current information on the participation of zinc and matrix metalloproteinases types 2 and 9 in mechanisms involved in the pathogenesis of breast cancer. We conducted a literature review, in consultation with the PubMed, Lilacs, and Scielo databases. The zinc and cysteine residues are structural elements shared by all members of the family of matrix metalloproteinases, and these proteins appear to be involved in the propagation of various types of neoplasms, including breast cancer. Moreover, transported zinc is likely to be used for the metalation of the catalytic domain of the newly synthesized metalloproteinases before the latter are secreted. Accordingly, increase in zinc concentrations in cellular compartments and the reduction of this trace element in the blood of patients with breast cancer appear to alter the activity of metalloproteinases 2 and 9, contributing to the occurrence of malignancy. Thus, it is necessary to carry out further studies with a view to clarify the role of zinc and metalloproteinases 2 and 9 in the pathogenesis of breast cancer.

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“…Verrucous carcinoma (VC) is considered to be an uncommon exophytic distinctive low-grade well differentiated pathological variant of OSCC (3) . Cancer is a multifactorial, multifaceted, and multimechanistic disease requiring a multidimensional approach for its diagnosis, treatment, and prevention (4) . Over the past decade, several studies have shown that the microenvironment or stroma of neoplastic tissues plays an active role in tumor progression.…”

Section: Introductionmentioning

confidence: 99%

Immunohistochemical Distribution of Myofibroblasts in Oral Squamous Cell Carcinoma, Verrucous Carcinoma and Oral Epithelial Dysplasia”

Majeed¹,

Yass²,

Sarkis³

2014

Iraqi dent. j.

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Background: Squamous cell carcinoma (SCC) is the most frequent type of oral malignancy that exhibits certain histological variations and is associated with a high mortality rate .Verrucous carcinoma (VC) is considered to be an uncommon exophytic distinctive low-grade well differentiated pathological variant of OSCC. Several studies have shown that the microenvironment or stroma of neoplastic tissues plays an active role in tumor progression. Concurrent with the conversion of non-diseased epithelial tissue to pre-cancerous epithelium to carcinoma, the stroma also changes from normal to primed (activated or tumor associated). Objective: The aim of this study was to compare the distribution of myofibroblasts in normal oral mucosa, oral epithelial dysplasia, verrucous carcinoma, and different histological grades of OSCC. Materials and methods: Twenty four formalin -fixed, paraffin -embedded tissue blocks (10 cases oral squamous cell carcinoma, 8 cases oral epithelial dysplasia and 6 cases verrucous carcinoma) were included in this study. An immunohistochemical analysis was performed using anti alpha -smooth muscle actin (a-SMA) monoclonal antibody. Results: All cases of OSCC, intraoral dysplasia and verruous carcinoma, and normal oral mucosa showed positive reaction of actin in the stromal smooth muscles surrounding blood and lymphatic vessels. All OSCCs demonstrated stromal immunostaining for a-SMA with different scores indicating the presence of myofibroblast. There were no myofibroblasts in the stroma of normal mucosa, epithelial dysplasia or verrucuos carcinoma samples indicated by negative a-SMA expression in them. Conclusion:The lack of myofibroblasts in normal, dysplastic oral epithelium and VC and their appearance in OSCC, suggests that the genetically altered epithelium (carcinomatous epithelium), besides the invasive behaviour of OSCC may have an inductive effect on the adjacent stroma to produce myofibroblasts.

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Clinical significance of MMP‐2 and MMP‐9 in patients with oral cancer

Abstract: The data indicate that MMP-2 and MMP-9 can be useful to identify metastatic phenotype as well as for treatment monitoring in oral cancer.

Cited by 120 publications

References 28 publications

Expression of FLJ10540 is correlated with aggressiveness of oral cavity squamous cell carcinoma by stimulating cell migration and invasion through increased FOXM1 and MMP-2 activity

Expression of FLJ10540 is correlated with aggressiveness of oral cavity squamous cell carcinoma by stimulating cell migration and invasion through increased FOXM1 and MMP-2 activity

Zinc and metalloproteinases 2 and 9: What is their relation with breast cancer?

Immunohistochemical Distribution of Myofibroblasts in Oral Squamous Cell Carcinoma, Verrucous Carcinoma and Oral Epithelial Dysplasia”

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