Activity of Matrix Metalloproteinases‐2 and ‐9 in Advanced Laryngeal Cancer

Bogusiewicz, Michał; Stryjecka-Zimmer, Marta; Szymański, Marcin; Rechberger, Tomasz; Gołąbek, Wiesław

doi:10.1067/mhn.2003.8

Cited by 21 publications

(20 citation statements)

References 18 publications

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“…[45][46][47] Although most studies evaluate MMP mRNA or immunohistochemical reactivity, which may not correspond to in vivo enzymatic activity, increased active MMP-2 and MMP-9 has prognostic importance in laryngeal SCC 48,49 and oral cavity SCC. 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.…”

Section: Assessment Of Matrix Metalloproteases In Head and Neck Cancermentioning

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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Section: Assessment Of Matrix Metalloproteases In Head and Neck Cancermentioning

confidence: 99%

Matrix metalloproteases in head and neck cancer

Rosenthal¹,

2006

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“…Elevated expression and activation of MMP-2 and MMP-9 are reported to be related to the aggressiveness and overall patient survival in several human tumors (Manenti et al 2003). It is suggested that both activated forms of MMP-2 and MMP-9 are involved in the expansion of laryngeal cancers, and that activated MMP-2 plays an important role in the lymphatic spread of the cancers (Bogusiewicz et al 2003). In renal cell carcinoma the poor survival and high frequency of metastasis are reported to be associated with both MMP-9 transcript overexpression and high gelatinolytic activity (Cho et al 2003).…”

Section: Introductionmentioning

confidence: 98%

Matrix metalloproteinases 2 and 9 in oral squamous cell carcinomas: manifestation and localization of their activity

Kato

Hara

Kuno

et al. 2004

J Cancer Res Clin Oncol

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These results indicate that two types of proform and activated form matrix metalloproteinases, MMP-2 and MMP-9, are present in human OSCC, and that the activated MMP-2 could be a main enzymatic activity of gelatinolysis in OSCC. Interaction of tumor cells and stromal cells seems to play an important role in the invasion and metastasis of human OSCC. Combination analysis of zymography and FIZ is a useful method to detect activity and localization of MMPs in human OSCC.

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“…gelatinase-A (MMP-2) and gelatinase-B (MMP-9) have the capacity to degrade the triple helix type IV and V collagen of the basement membrane, thus contributing to the invasion and metastases of malignant tumors [23]. Most studies have focused on the prognostic value of MMP expression in laryngeal squamous cell carcinoma growth and spreading to the lymph nodes [24][25][26][27].…”

Section: Introductionmentioning

confidence: 99%

Expression of matrix metalloproteinases (MMP-2 and MMP-9) in recurrent respiratory papillomas and laryngeal carcinoma: clinical and morphological parallels

Uloza¹,

Liutkevičius²,

Pangonytė

et al. 2011

Eur Arch Otorhinolaryngol

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The task of the present study was to investigate the expression of MMP-2 and MMP-9 in recurrent respiratory papillomas (RRP) and accomplish a comparative analysis with those in laryngeal squamous cell carcinoma (LSCC). The immunohistochemical expression of MMP-2 and MMP-9 was investigated in specimens taken from RRP (n = 38) and LSCC (n = 39) patient groups, and the normal tissue of vocal fold (n = 12, control group). The expression of MMP-2 and MMP-9, both in epithelium and stroma cells, was graded on a semiquantitative scale, ranging from 0 (no expression) to 18 points (high expression). Statistically significant differences in the expression of MMP-2 and MMP-9, both in epithelium and stroma among the RRP, LSCC patients and control group (epithelium) with the LSCC group having the highest MMPs expression scores were revealed. However, no statistically significant correlations among expression of MMPs and clinical and/or morphological features were found in the group of RRP patients. The MMP-2 stroma value of 10.4 points was determined as the optimum point (limiting value) for separating RRP and LSCC patient groups. Results of the present study indicate that the expression of both MMP-2 and MMP-9 are up-regulated early in development of laryngeal papillomas, when the benign neoplastic lesion begins and the next determinant step is concerned with the occurrence of malignization. These results seem promising, as they may improve our understanding of the molecular events leading to the papilloma formation and development, however, further research is needed.

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Activity of Matrix Metalloproteinases‐2 and ‐9 in Advanced Laryngeal Cancer

Abstract: Results of the study indicate that both MMP-2 and MMP-9 may be involved in the expansion of laryngeal cancer. MMP-2 may also play an important role in the lymphatic spread of some laryngeal tumors.

Cited by 21 publications

References 18 publications

Matrix metalloproteases in head and neck cancer

Matrix metalloproteases in head and neck cancer

Matrix metalloproteinases 2 and 9 in oral squamous cell carcinomas: manifestation and localization of their activity

Expression of matrix metalloproteinases (MMP-2 and MMP-9) in recurrent respiratory papillomas and laryngeal carcinoma: clinical and morphological parallels

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