Membrane-type matrix metalloproteinase (MT-MMP) gene is expressed in stromal cells of human colon, breast, and head and neck carcinomas.

Okada, Akiko; Bellocq, Jean‐Pierre; Rouyer, Nicolas; Chenard, Marie–Pierre; Rio, Marie‐Christine; Chambon, Pierre; Basset, Paul

doi:10.1073/pnas.92.7.2730

Cited by 447 publications

(353 citation statements)

References 17 publications

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“…They have been shown to be of interest in breast carcinoma with the former showing a distribution similar to MMP-2, and to correlate with increasing tumour stage (Ueno et al, 1997). Elevated expression of MT1-MMP has been reported in a variety of solid tumours including cervix (Gilles et al, 1996), head and neck and colon (Okada et al, 1995). In tissues from 41 patients with bladder cancer, using nonquantitative RT -PCR, MT1-MMP was shown to associate strongly with decreased survival (Kanayama et al, 1998).…”

Section: Discussionmentioning

confidence: 99%

Comprehensive profiling and localisation of the matrix metalloproteinases in urothelial carcinoma

et al. 2006

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The matrix metalloproteinases (MMPs) are endopeptidases which break down the extracellular matrix and regulate cytokine and growth factor activity. Several MMPs have been implicated in the promotion of invasion and metastasis in a broad range of tumours including urothelial carcinoma. In this study, RNA from 132 normal bladder and urothelial carcinoma specimens was profiled for each of the 24 human MMPs, the four endogenous tissue inhibitors of MMPs (TIMPs) and several key growth factors and their receptors using quantitative real time RT -PCR. Laser capture microdissection (LCM) of RNA from 22 tumour and 11 normal frozen sections was performed allowing accurate RNA extraction from either stromal or epithelial compartments. This study confirms the over expression in bladder tumour tissue of well-documented MMPs and highlights a range of MMPs which have not previously been implicated in the development of urothelial cancer. In summary, MMP-2, MT1-MMP and the previously unreported MMP-28 were very highly expressed in tumour samples while MMPs 1, 7, 9, 11, 15, 19 and 23 were highly expressed. There was a significant positive correlation between transcript expression and tumour grade for MMPs 1, 2, 8, 10, 11, 12, 13, 14, 15 and 28 (Po0.001). At the same confidence interval, TIMP-1 and TIMP-3 also correlated with increasing tumour grade. LCM revealed that most highly expressed MMPs are located primarily within the stromal compartment except MMP-13 which localised to the epithelial compartment. This work forms the basis for further functional studies, which will help to confirm the MMPs as potential diagnostic and therapeutic targets in early bladder cancer.

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Section: Discussionmentioning

confidence: 99%

Comprehensive profiling and localisation of the matrix metalloproteinases in urothelial carcinoma

et al. 2006

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“…Several MMPs including MMP-2, MMP-11 and MMP-14 are expressed by fibroblast-like cells in human colon cancer, 27,31,[42][43][44] some of which may indeed be myofibroblasts. The role of the (myo-) fibroblasts in colon cancer progression is not known.…”

Section: Discussionmentioning

confidence: 99%

Localization of tissue inhibitor of metalloproteinases 1 (TIMP‐1) in human colorectal adenoma and adenocarcinoma

Holten-Andersen

Hansen

Brünner³

et al. 2004

Intl Journal of Cancer

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Tissue inhibitor of matrix metalloproteases 1 (TIMP-1) inhibits the proteolytic activity of matrix metalloproteases and hereby prevents cancer invasion. However, TIMP-1 also possesses other functions such as inhibition of apoptosis, induction of malignant transformation and stimulation of cell-growth. We have previously demonstrated that TIMP-1 is elevated in blood from colorectal cancer patients and that high TIMP-1 levels predict poor prognosis. To clarify the role of TIMP-1 in colorectal tumorigenesis, the expression pattern of TIMP-1 in benign and malignant colorectal tumors was studied. In all of 24 cases of colorectal adenocarcinoma TIMP-1 mRNA was detected by in situ hybridization. In all cases TIMP-1 expression was found in fibroblast-like cells located at the invasive front but was seen only sporadically in normal mucosa. No TIMP-1 mRNA was seen in any of the cases in benign or malignant epithelial cells, in vascular cells or smooth muscle cells. Comparison of sections processed for TIMP-1 in situ hybridization with sections immunohistochemically stained with antibodies against TIMP-1 showed good correlation between TIMP-1 mRNA and immunoreactivity. Combining TIMP-1 in situ hybridization with immunohistochemical staining for ␣-smooth muscle actin or CD68 showed TIMP-1 mRNA in myofibroblasts but not in macrophages. TIMP-1 mRNA was detected in 2 of 7 adenomatous polyps in the adenoma area: in both cases associated with focal stromal inflammation at the epithelial-stromal interface. In conclusion, TIMP-1 expression is a rare event in benign human colon tissue but is highly expressed by myofibroblasts in association with invading colon cancer cells.

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“…13,50-52 Although MT1-MMP can degrade type I collagen and other matrix components, 29 MT1-MMP also activates MMP-2 and is, therefore, considered a critical enzyme controlling proteolytic activity. 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.…”

Section: Assessment Of Matrix Metalloproteases In Head and Neck Cancermentioning

confidence: 99%

“…Indeed, one of the first reports of MT-1 expression in human cancers was in head and neck cancer. 54 Elevated MT1-MMP expression in HNSCC has been shown to positively correlate with an aggressive pattern of invasion, poor survival, and lymph node metastasis. 12,[76][77][78] Increased activity of the MT1-MMP activator, furin, is associated with more aggressive in vitro and in vivo tumor activity in HNSCC.…”

Section: Mt1-mmp As a Target For Selective Inhibition In Head And Necmentioning

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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Membrane-type matrix metalloproteinase (MT-MMP) gene is expressed in stromal cells of human colon, breast, and head and neck carcinomas.

Abstract: ABSTRACT

Cited by 447 publications

References 17 publications

Comprehensive profiling and localisation of the matrix metalloproteinases in urothelial carcinoma

Comprehensive profiling and localisation of the matrix metalloproteinases in urothelial carcinoma

Localization of tissue inhibitor of metalloproteinases 1 (TIMP‐1) in human colorectal adenoma and adenocarcinoma

Matrix metalloproteases in head and neck cancer

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