Matrix metalloproteinases in head and neck cancer: current perspectives

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.

Molecular markers associated with development and progression of potentially premalignant oral epithelial lesions: Current knowledge and future implications

“…90,91 Matrix metalloproteinases (MMPs) constitute a family of zinc-dependent endopeptidases, further subdivided into collagenases, stromelysins, gelatinases, matrilysins, metalloelastase, membrane-type MMPs, and others, capable of digesting various extracellular matrix constituents. 92,93 In addition to enabling and facilitating tumor cell invasion, MMPs also participate in oncogenic tumor signaling by modulating the availability of growth factor and cell surface receptors. 93 Overexpression of MMPs has been shown to be associated with tumor invasion in several malignancies, including OSCC.…”

“…92,93 In addition to enabling and facilitating tumor cell invasion, MMPs also participate in oncogenic tumor signaling by modulating the availability of growth factor and cell surface receptors. 93 Overexpression of MMPs has been shown to be associated with tumor invasion in several malignancies, including OSCC. For example, several studies have highlighted a role for MMP-9 in oral cancer, including its potential usefulness as a marker of poor prognosis, associated with regional lymph node and/or distant metastasis.…”

Anti‑photoaging effect of fermented agricultural by‑products on ultraviolet B‑irradiated hairless mouse skin

“…MMPs are zinc-dependent endopeptidases that are formed via the UVB irradiation-induced activation of MAPK signaling pathway transcription factors. Functionally, MMPs are classified as stromelysins (including MMP-3, -10 and -11), gelatinases (MMP-2 and -9) and collagenases (MMP-1, -8 and -13) on the basis of their substrate specificity (36). Stromelysins may cleave type IV collagen, in addition to proteoglycans, laminin and fibronectin (37).…”

ECM Remodeling in Squamous Cell Carcinoma of the Aerodigestive Tract: Pathways for Cancer Dissemination and Emerging Biomarkers

“…The cleavage of the pro-domain results in MMP activation and occurs in the pericellular space in an integrin-dependent manner (e.g., for pro-MMP2) or intracellularly due to the activity of furin-like proprotein convertases (e.g., for MT-MMPs) [ 213 ]. The catalic domain possesses a zinc (Zn 2+ ) active site linked to the hemopexin-like C-terminal portion [ 214 , 215 ], which determines the substrate specificity [ 216 , 217 ]. MMPs are capable of cleaving a number of ECM components, resulting in their degradation and, often, the release of active fragments, as for instance demonstrated for collagen XVIII, perlecan and agrin [ 135 , 138 , 154 ].…”