Expression of MMPS, MT‐MMP, and TIMPs in squamous cell carcinoma of the oral cavity: Correlations with tumor invasion and metastasis

Kurahara, Shinichi; Shinohara, Masanori; Ikebe, Tetsuro; Nakamura, Seiji; Beppu, Mahiro; Hiraki, Akimitsu; Takeuchi, Hiroshi; Shirasuna, Kanemitsu

doi:10.1002/(sici)1097-0347(199910)21:7<627::aid-hed7>3.3.co;2-u

Cited by 93 publications

(175 citation statements)

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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%

“…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 tumors and adjacent normal specimens.…”

Section: Assessment Of Matrix Metalloproteases In Head and Neck Cancermentioning

confidence: 99%

“…53 HNSCC was one of the first tumors in which MT1-MMP was identified, 54 and MT1-MMP expression is reported in 75% to 100% of HNSCC tumors. 22,55 Although the focus of this review is on MMPs, other proteases have been demonstrated to play a role in head and neck cancer. Plasmin is a broad-spectrum protease best known for its role in fibrin degradation in wound healing, and the urokinase-plasminogen axis has frequently been identified as agents that promote both tumor invasion and angiogenesis.…”

Section: Assessment Of Matrix Metalloproteases In Head and Neck Cancermentioning

confidence: 99%

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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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Section: Matrix Metalloproteasesmentioning

confidence: 99%

Section: Assessment Of Matrix Metalloproteases In Head and Neck Cancermentioning

confidence: 99%

Section: Assessment Of Matrix Metalloproteases In Head and Neck Cancermentioning

confidence: 99%

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Matrix metalloproteases in head and neck cancer

Rosenthal¹,

2006

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“…22 Some studies have suggested an association between gelatinase mRNA, immunoreactive protein or enzyme activity with invasion or lymph node metastasis in some tumor types according to their malignancy category. [23][24][25] However, the data relating to the significance of circulating MMP-9 in patients with HNSCC as a prognostic marker have been less studied. The present study was conducted to measure preoperative or pretreatment serum MMP-9 levels in patients with head and neck squamous cell carcinoma and to correlate them with clinical behavior and disease outcome as well as to study whether the circulating MMP-9 levels would correlate to MMP-9 immunohistochemical staining in the corresponding primary tumor or to the tumor burden.…”

mentioning

confidence: 99%

Serum matrix metalloproteinase‐9 in head and neck squamous cell carcinomais a prognostic marker

Ruokolainen

Pääkkö

Turpeenniemi‐Hujanen

2005

Intl Journal of Cancer

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The aim of this study was to determine whether serum matrix metalloproteinase-9 (MMP-9) could predict cause-specific and relapse-free survival in patients with squamous cell carcinoma of head and neck. Furthermore, this study was designed to investigate whether there is an association between MMP-9 immunohistochemical staining and serum MMP-9 levels. Pretreatment serum levels of MMP-9 were quantitatively measured by ELISA assay in 67 patients presenting with a primary head and neck squamous cell carcinoma. The results were compared with the corresponding immunohistochemical staining results, clinical data and the patients' outcome. The follow-up time for all of the patients was at least 5 years. There was a statistically significant correlation between circulating MMP-9 and MMP-9 immunohistochemical staining in the corresponding tumors (p 5 0.028). The cause-specific and relapse-free survival rates were clearly lower among patients with high MMP-9 serum levels (> 73 ng/ml). The 5-year cause-specific survival-rate was 40% in a patient group with high serum MMP-9, and 69% for patients with a low MMP-9 level (p 5 0.027). In the same follow-up period, the cumulative relapsefree survival rate was 36% in patients presenting with a high serum MMP-9 and 66% in those with a low MMP-9 level. No correlation was found between MMP-9 serum levels and the traditional clinical or histopathologic factors. The results suggest for the first time that pretreatment serum MMP-9 level could serve as a prognostic factor in head and neck squamous cell carcinoma. ' 2005 Wiley-Liss, Inc.

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“…The expression of MMPs in head and neck cancers has been reported. [4][5][6][7][8][9][10][11][12][13][14] Those studies demonstrated that immunoreactive MMP-2 and MMP-9 staining was stronger in patients with lymph node metastasis and was associated with lower survival rates. [11][12][13][14] MMP-7 is one of the few MMPs overexpressed by carcinoma cells rather than by stromal cells.…”

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confidence: 99%

Active matrix metalloproteinase-7 is associated with invasion in buccal squamous cell carcinoma

Chuang

Huang

et al. 2008

Modern Pathology

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Protein microarrays have shown that matrix metalloproteinase-7 is upregulated in head and neck squamous cell carcinomas, but its role in local tissue invasion is still uncertain. We investigated the expression of active matrix metalloproteinase-7, using tissue microarray, immunohistochemistry, and western blotting, in oral tissues from 24 patients with buccal squamous cell carcinoma, and correlated the findings with clinicopathological features. Normal buccal tissue samples from the same patients, obtained at sites at least 1 cm from tumor tissue, served as normal controls. Total matrix metalloproteinase-7 was detected on western blots in 9 of 15 (60%) tumor tissue samples and in 2 of 15 (13%) normal mucosal samples; this difference was significant (P ¼ 0.008). Moreover, the active matrix metalloproteinase-7 was expressed only in eight of the nine (89%) tumor samples that expressed matrix metalloproteinase-7, and in none of the normal tissue samples, regardless of the expression status of the pro-matrix metalloproteinase-7. Immunostaining of matrix metalloproteinase-7 was observed histologically in both tumor and nonneoplastic epithelium, but immunostaining of active matrix metalloproteinase-7 was present only in tumor nests. Expression of active matrix metalloproteinase-7 was associated with larger tumor size (P ¼ 0.022) and was significantly higher in buccal squamous cell carcinoma with adjacent skin or bone invasion (P ¼ 0.036). In conclusion, active matrix metalloproteinase-7 expression was associated with more aggressive buccal squamous cell carcinomas.

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Expression of MMPS, MT‐MMP, and TIMPs in squamous cell carcinoma of the oral cavity: Correlations with tumor invasion and metastasis

Cited by 93 publications

References 0 publications

Matrix metalloproteases in head and neck cancer

Matrix metalloproteases in head and neck cancer

Serum matrix metalloproteinase‐9 in head and neck squamous cell carcinomais a prognostic marker

Active matrix metalloproteinase-7 is associated with invasion in buccal squamous cell carcinoma

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