Matrix metalloproteinase (MMP)-7, also known as matrilysin, is a "minimal domain MMP" that exhibits proteolytic activity against components of the extracellular matrix (ECM). Matrilysin is frequently overexpressed in human cancer tissues and is associated with cancer progression. Tumorigenesis is a multistep process involving cell growth, invasion, metastasis, and angiogenesis. Matrilysin has been shown to play important roles not only in degradation of ECM proteins, but also in the regulation of several biochemical processes such as activation, degradation, and shedding of non-ECM proteins. This minire-view provides a summary of the current literature on the roles of matrilysin in tumorigenesis with a focus on the roles of modifications of non-ECM proteins by matrilysin and other related MMPs in tumorigenesis. Proteolysis of insulin-like growth factor binding protein by matrilysin results in increased bioavailability of insulin-like growth factors and enhanced cellular proliferation. Matrilysin has also been implicated in the ectodomain shedding of several cell surface molecules. Heparin-binding epidermal growth factor precursor (proHB-EGF) is cleaved by matrilysin into mature HB-EGF, which promotes cellular proliferation. Membrane-bound Fas ligand (FasL) is cleaved into soluble FasL, which increases apoptosis of cells adjacent to tumor cells. E-cadherin is converted to soluble E-cadherin to promote invasion. Tumor necrosis factor (TNF)-alpha precursor is cleaved to release soluble TNF-alpha to increase apoptosis. We propose that these matrilysin-mediated pathways provide the necessary and logical mechanisms to promote cancer progression.

Abstractp53 is the most frequently mutated tumor suppressor gene in human neoplasia and encodes a transcriptional coactivator.

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Head and neck squamous cell carcinoma (HNSCC) is a cancer of the upper aerodigestive tract. The condition is subdivided to some potential anatomic sites such as maxilla, oropharynx, larynx and hypopharynx. Although treatment guidelines have been developed according to tumor site, tumor-node-metastasis (TNM) stage and histologic diagnosis, they do not always predict clinical outcome accurately. 1 Identification of better prognostic markers would allow selection of high-risk patients for closer surveillance or more intensive treatment. Poor outcome is often the result of local recurrence and distant metastasis. 1 Therefore, factors that represent the potential of invasion and metastasis such as expression of matrix metalloproteinases (MMPs) could predict prognosis of HNSCC.In the multistep theory of metastasis, degradation of surrounding stroma, especially basement membrane, is an initial step. MMPs degrade various extracellular matrix (ECM) components. 2,3 Each MMP has different substrate specificity. MMP2 and MMP9 are capable of degrading type IV collagen, which is a major component of basement membrane. Expression of these MMPs has been reported to correlate with tumor metastasis in various cancers. 4 -7 Previously, we reported that expression of MMP-2 and MT1-MMP is a common feature of HNSCC. 7 MMP-2 is secreted in an inactive zymogen form (pro-MMP2) and is converted to an active form (active-MMP2) by membrane type 1-metalloproteinase (MT1-MMP). 8 Tissue inhibitor of metalloproteinase 2 (TIMP-2) was originally identified as an inhibitor of MMP and thus expected to be a negative factor for tumor invasion. 2,3 However, a recent biochemical analysis demonstrated that TIMP-2 could contribute to activation of MMP-2. 9,10 Now it is a matter of importance whether TIMP-2 expression correlates positively or negatively with invasive and metastatic potential of tumors. [11][12][13][14][15] This study was designed to evaluate the relationship and the prognostic value of MMP-2, MT1-MMP and TIMP-2 proteins in tongue SCC. PATIENTS AND METHODS Patient characteristicsThe data used in this study were obtained from medical records. Sixty-three tongue SCC patients, initially diagnosed at the Kanazawa University Hospital, Kanazawa, Japan and the Central Hospital of Toyama Pref. Toyama, Japan between January 1988 and December 1993, were included in the present study. Nine patients who were treated by chemotherapy and radiation therapy, and 2 patients treated by chemotherapy alone were excluded. One patient with distant metastasis was also excluded. Thus, 51 patients who were treated with surgery remained. Therapeutic neck dissection was performed on 22 patients who had clinically positive nodes. Supraomohyoid neck dissection was performed on 17 patients with clinically negative nodes who had T2 or more advanced tumor status. Twelve patients did not undergo neck dissection because of stage I disease. Postoperative radiotherapy (60 -70 Gy) was administered to the neck of patients with pathologically positive lymph node metastasis. ...

These results suggest that MT1-MMP is involved in the activation of pro-MMP2 in HNSCC. These findings suggest that MT1-MMP is significant not only as a tumor marker but as a new target for chemotherapy against HNSCC.