Elevated expression of MMP-13 and TIMP-1 in head and neck squamous cell carcinomas may reflect increased tumor invasiveness.

Nil Culhaci,Eray Copcu,Kubilay Metin,Emel Dikicioglu

doi:10.1186/1471-2407-4-42

Abstract

BackgroundMatrix metalloproteinases [MMPs], which degrade the extracellular matrix, play an important role in the invasion and metastasis of squamous cell carcinomas. One MMP, MMP-13, is thought to play a central role in MMP activation. The purpose of this study was to investigate MMP-13 and TIMP-1 expression in squamous cell carcinomas of the head and neck and to relate these levels of expression to histologic patterns of invasion.MethodsThis study included T1 lesions obtained via biopsy from the larynx, tongue, and skin/mucosa of 78 patients with head and neck squamous cell carcinomas. The relationship between expression of MMP-13 and TIMP-1 and the mode of tumor invasion [MI] was evaluated immunohistochemically, using breast carcinoma tissue as a positive control.ResultsIncreased expression was observed in highly invasive tumors, as reflected by the significant correlation between the degree of staining for MMP-13 or TIMP-1 and MI grade [p < 0.05]. There was no significant relationship between the degree of staining for MMP-13 or TIMP-1 and patient age, sex, tumor site, or tumor histologic grade. In addition, levels of staining for MMP-13 did not correlate with levels of staining for TIMP-1.ConclusionThe expression of MMP-13 and TIMP-1 appears to play an important role in determining the invasive capacity of squamous cell carcinomas of the head and neck. Whereas additional studies are needed to confirm these findings, evaluating expression of these MMPs in small biopsy samples may be useful in determining the invasive capacity of these tumors at an earlier stage.

Highlights

Matrix metalloproteinases [MMPs], which degrade the extracellular matrix, play an important role in the invasion and metastasis of squamous cell carcinomas
MMP-13, which plays a central role in MMP activation, has been shown to be highly expressed in head and neck SCCs [HNSCCs] [5]
We characterized the expression of one MMP–MMP-13, which plays a key role in the MMP activation cascade–and one inhibitor of MMPs, TIMP-1, in HNSCCs

Summary

Introduction

Matrix metalloproteinases [MMPs], which degrade the extracellular matrix, play an important role in the invasion and metastasis of squamous cell carcinomas. The invasion of surrounding tissues by neoplastic cells is one of the most important steps in tumor progression Proteolytic enzymes such as matrix metalloproteinases [MMPs] contribute to tumor expansion by degrading components of the extracellular matrix [ECM]. MMPs are a 21-member family of zinc-dependent endopeptidases, which are capable of degrading most ECM components including collagen, elastin, fibronectin, and gelatin. Whereas this facilitates processes such as wound healing, enhanced MMP activity has been observed in a variety of (page number not for citation purposes). Elevated MMP-13 expression has been found in a number of different malignancies, and expression has been related to tumor behavior and patient prognosis [7,9,10]

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