Activation of MMP‐2 and MMP‐9 in patients with oral squamous cell carcinoma

Patel, Beena P.; Shah, Pankaj; Rawal, Upendra M.; Desai, Amisha; Shah, Sonal Patel; Rawal, Rakesh; Patel, Prabhudas S

doi:10.1002/jso.20240

Cited by 100 publications

(81 citation statements)

References 25 publications

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“…Our results from the tissue confirm that circulating levels of MMPs and TIMPs are reflecting the direct tissue situation. Also significantly increased levels of latent, active and total forms of MMP-2 and MMP-9 strengthen results we have obtained in our lab in an earlier study in oral cancer and breast cancer with tissue as specimens [28,29].…”

Section: Rt-pcr Results For Mmps and Timpssupporting

confidence: 88%

Matrix Metalloproteinases and Their Inhibitors: Correlation with Invasion and Metastasis in Oral Cancer

Haridas

Patel

et al. 2010

Indian J Clin Biochem

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Matrix metalloproteinases (MMPs) have been implicated in invasion and metastasis of various malignancies. The study evaluated a comprehensive profile of MMP-2 and MMP-9 and their inhibitors, tissue inhibitor of metalloproteinases-2 (TIMP-2) and tissue inhibitor of metalloproteinases-1 (TIMP-1), respectively in 50 controls and 75 patients with oral squamous cell carcinoma (OSCC). Blood samples from controls and patients as well as malignant and adjacent normal tissues from the patients were collected. The study examined pro, active and total forms of MMP-2 and MMP-9 using zymography. Enzymelinked immunoassay (ELISA) and reverse transcription polymerase chain reaction were carried out to evaluate protein levels and mRNA expression; respectively, for the MMPs and TIMPs. Plasma pro, active and total MMP-2, MMP-9 as well as TIMP-1 and TIMP-2 levels were significantly higher in oral cancer patients as compared to the controls. mRNA expression of the MMPs and TIMPs was significantly higher in malignant tissues as compared to adjacent normal tissues. A significant positive correlation was observed between levels of proMMP-9 and active MMP-9 with differentiation, stage and infiltration. ProM-MP-2 and active MMP-2 exhibited significant positive correlation with differentiation and lymph node involvement. The multivariate analysis of ELISA results revealed a significant positive correlation between MMP-2, TIMP-1 and TIMP-2 levels with lymph node involvement, stage and differentiation. The receiver operating characteristic curve (ROC) analysis showed that the levels of MMPs and TIMPs have significant discriminatory efficacy to differentiate between controls and patients. The results indicate that MMP-2, MMP-9, TIMP-1 and TIMP-2 have significant clinical usefulness for oral cancer patients. Zymographic analysis is a simple, cost effective, rapid and sensitive alternative assay.

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Section: Rt-pcr Results For Mmps and Timpssupporting

confidence: 88%

Matrix Metalloproteinases and Their Inhibitors: Correlation with Invasion and Metastasis in Oral Cancer

Haridas

Patel

et al. 2010

Indian J Clin Biochem

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“…The DNAzyme inhibited both SCC cell growth and tumor angiogenesis. Dz13 blocked MMP-2 and MMP-9 expression in vitro and in vivo, both of which are capable of degrading type 4 collagen, a major component of basement membrane and are found activated in SCC patients (Patel et al, 2005). Although MMP-2 and MMP-9 are suppressed by Dz13, it is possible that c-Jun also regulates SCC growth through other MMPs.…”

Section: Dz13 Inhibits Mmp-2 Expression In Scc Tumorsmentioning

confidence: 96%

Squamous cell carcinoma growth in mice and in culture is regulated by c-Jun and its control of matrix metalloproteinase-2 and -9 expression

Zhang

Luo

Sumithran³

et al. 2006

Oncogene

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“…These enzymes are capable of cleaving most ECM components, as well as other biologically important proteins such as growth factors, other proteases, adhesion molecules, and cell surface receptors (Table 1). [9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26] With a widening understanding of MMP substrates, a more complex role for these enzymes in tumor growth and metastasis has been appreciated.…”

Section: Matrix Metalloproteasesmentioning

confidence: 99%

Matrix metalloproteases in head and neck cancer

Rosenthal¹,

2006

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Matrix metalloproteases (MMPs) are a collection of enzymes capable of cleaving extracellular matrix components, growth factors, and cell-surface receptors. MMPs modulate most aspects of tumorigenesis and are highly expressed in cancer compared with normal tissues. Preclinical studies have demonstrated that head and neck squamous cell carcinomas (HNSCCs) express high levels of MMPs in vivo and that inhibition of these enzymes in vitro and in mouse models decreases invasion and metastasis. However, the clinical trials for MMP inhibitors have failed to demonstrate a significant survival advantage in most cancers. The disparity between preclinical and clinical studies has led to the reevaluation of how MMP functions in cancer and the design of clinical trials for molecularly targeted agents. Mouse model data and analysis of HNSCC tumor specimens suggests that membrane type-1 MMP (MT1-MMP) may be a critical enzyme in tumor cell invasion and survival in vivo. This accumulated data provide evidence for development of selective MT1-MMP inhibitors as therapy in HNSCC.Keywords matrix metalloprotease inhibitor; MMP; extracellular matrix; head and neck cancer; squamous cell carcinoma; membrane type-1 MMP; drug development; proteases The hallmark of cancer remains regional and distant metastases. Regional metastasis in head and neck squamous cell carcinoma (HNSCC) decreases survival by almost 50%, and invasion beyond the lymph node capsule further decreases survival. 1 For tumor cells to invade and metastasize they must: (1) develop motility, (2) alter cell-cell and cell-matrix adhesion, and (3) remodel the extracellular matrix. 2 It was recognized in the 1980s that matrix metalloprotease (MMP) could degrade extracellular matrix (ECM) components and that this could potentiate local tumor invasion and metastasis. 3 A significant amount of effort has been funneled into the development of MMP inhibitors (MPIs) promote tumor angiogenesis by mobilizing or activating factors such as basic fibroblast growth factor, vascular endothelial growth factor, or transforming growth factor-beta. 15,16,18 Second, the complexity of cell types expressing MMPs in the tumor mass was appreciated ( Figure 1 ASSESSMENT OF MATRIX METALLOPROTEASES IN HEAD AND NECK CANCERMMPs consistently found overexpressed in head and neck cancer include MMP-1, MMP-2, MMP-3, MMP-7, MMP-8, MMP-9, MMP-10, MMP-11, MMP-13, and MMP-14 (Table 1). However, MMP-1, MMP-2, MMP-9, and MT-1 MMP are most commonly identified in HNSCC and associated with disease progression. With the understanding that conflicting reports are abundant and negative studies unlikely to be published, it is possible to summarize the extensive MMP findings in HNSCC. Although most studies evaluate only one or two MMPs within a given head and neck site, studies have examined expression of multiple TIMPs and MMPs in oral cavity SCC. 12,22 Interestingly, these studies commonly identify upregulation of TIMP-1, which is associated with a poor survival. Levels of TIMP-2 are often unchanged between t...

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Activation of MMP‐2 and MMP‐9 in patients with oral squamous cell carcinoma

Cited by 100 publications

References 25 publications

Matrix Metalloproteinases and Their Inhibitors: Correlation with Invasion and Metastasis in Oral Cancer

Matrix Metalloproteinases and Their Inhibitors: Correlation with Invasion and Metastasis in Oral Cancer

Squamous cell carcinoma growth in mice and in culture is regulated by c-Jun and its control of matrix metalloproteinase-2 and -9 expression

Matrix metalloproteases in head and neck cancer

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