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Matrix metalloproteinases in head and neck cancer: current perspectives

Authors Gkouveris I, Nikitakis NG, Aseervatham J, Rao N, Ogbureke KUE

Received 5 December 2016

Accepted for publication 3 February 2017

Published 2 May 2017 Volume 2017:4 Pages 47—61

DOI https://doi.org/10.2147/MNM.S105770

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Lucy Goodman

Peer reviewer comments 2

Editor who approved publication: Dr Yoshifumi Itoh

Ioannis Gkouveris,1 Nikolaos G Nikitakis,2 Jaya Aseervatham,1 Nanditha Rao,1 Kalu UE Ogbureke1,2

1Department of Oral Pathology, School of Dentistry, National and Kapodistrian University of Athens, Athens, Greece; 2Department of Diagnostic and Biomedical Sciences, School of Dentistry, University of Texas Health Science Center at Houston, Houston, TX, USA

Abstract:
Matrix metalloproteinases (MMPs) are zinc-dependent endopeptidases encoded by 24 distinct genes. Their functions have been implicated in numerous normal and pathologic processes, including uterine involution and organogenesis, inflammation and wound healing, vascular and autoimmune disease progression. Pertinent to this review, the role of MMPs in cancer biology is fairly well researched and documented, and remains a subject of continuing intense investigation. Not only are several MMPs overexpressed in head and neck squamous cell carcinomas (HNSCCs), expression has been correlated with salient tumorigenic hallmarks, such as cell proliferation, angiogenesis, invasion, and metastasis. The utility of changes in the expression profile, as well as various MMP polymorphisms as potential prognostic markers in oral cancers and oral premalignant lesions, have been investigated. Furthermore, the potential therapeutic utility of targeting MMPs in cancer remains attractive, although outcomes in this respect appear so far to be less encouraging with respect to HNSCCs. Because of the disappointing results observed in clinical trials where MMP-targeting regimens for HNSCCs utilized broad-spectrum small MMP catalytic site inhibitors, investigators now envision new strategies for MMP-specific targeting based on the recognition of new noncatalytic MMP domains with distinct functions. This review provides an overview of MMP activities in general and in cancers, and an update of their activities in HNSCC. Specifically, their role in the development and progression of HNSCC and their function as signaling molecules is discussed. Finally, their role as potential prognostic biomarkers and therapeutic targets in HNSCC is revisited.

Keywords:
MMPs, head and neck cancers, HNSCCs, oral squamous cell carcinoma, prognosis, therapy

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