Expression of matrix metalloproteinase-9 in oral potentially malignant disorders: A systematic review

Abstract

Matrix metalloproteinase-9 (MMP-9) is an inducible enzyme. Oral potentially malignant disorders (OPMDs) are considered as the early tissue changes that happen due to various habits such as smoking tobacco, chewing tobacco or stress. This alteration in the tissues alters the expression of MMP-9. The rationale of the review is to know the expression of MMP-9 in OPMDs. Hand searching and electronic databases such as PubMed and ScienceDirect were done for mesh terms such as OPMDs and MMP-9. Eight articles were obtained, after applying inclusion and exclusion criteria. These articles were assessed with QUADAS and data were extracted and evaluated. The included eight studies were done in 182 oral squamous cell carcinoma cases, 430 OPMDs (146 oral lichen planus, 264 leukoplakia and 20 oral submucous fibrosis) and 352 healthy controls evaluated for MMP-9. MMP-9 expression was found to be elevated in tissue, serum and saliva samples of OPMDs than in healthy controls. There is only one study in each serum and saliva samples to evaluate MMP-9. Saliva being noninvasive and serum being minimally invasive, more studies need to be done in both serum and saliva to establish MMP-9 as an early diagnostic marker in OPMDs to know its potential in malignant transformation.

Salivary MMP-9 as a Biomarker for the Diagnosis of Oral Potentially Malignant Disorders and Oral Squamous Cell Carcinoma

“…MMPs can degrade the extracellular matrix. It is secreted by neutrophils, macrophages, and fibroblasts, on the stimulus provided by transforming growth factor β and interleukin-8 (Venugopal and Uma Maheswari, 2016). The MMP sustains the bioavailability of growth factors, thus aiding in the proliferation of cancerous cells.…”

“…MMPs can be classified as gelatinases, collagenases, stromelysins, and membrane-type MMPs (Wu et al, 2010;Hema Shree et al, 2019) due to their working mechanism which can lead to fragmentation of the FAS receptors, reduction of natural killer cells, and preventing apoptosis. They can have dual role in angiogenesis, increase the bioavailability of vascular endothelial growth factor receptor (VEGFR) (Venugopal and Uma Maheswari, 2016), active role in the cell-to-cell adhesion, cell-to-extracellular matrix adhesion, breakdown of collagen (type IV, V, VII, X), fibronectin and elastin, (Chen et al, 2008) disintegrate several proteins, chemokines, cytokines, and alter their receptors to regulate cell growth and inflammation (Henriques et al, 2012).…”

“…The proximity of saliva with the oral lesion helps it sustain detectable levels of MMP-9 and hence aids in diagnosis (Wu et al, 2010;Venugopal and Uma Maheswari, 2016). Serum (Mardani et al, 2014;Lotfi et al, 2015) and tissue MMP-9 (Katayama et al, 2004) has been studied previously, while studies on salivary MMP-9 are scant.…”

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

“…In a recent systematic review, MMP-9 levels were reported to be elevated in the tissue, serum, and saliva samples of PPOELs compared with controls. 96 However, the limited number of studies did not provide conclusive evidence regarding MMP-9 as a potential marker of MT risk in PPOELs. Besides, it has been proposed that MMP-9 may exhibit diverse oncogenic or tumor suppressive functions under different conditions, related to patient or tumor characteristics.…”

Evaluation of the therapeutic effect of topical calcipotriol versus topical tretinoin in treatment of oral Leukoplakia and their effect on clinical improvement and salivary level of MMP-9, IL-6 and TGF-β: A Randomized Clinical Trial

“…Matrix metallo-proteinases (MMPs) a group of enzymes secreted by macrophages, neutrophils and fibroblasts in response to the stimulus from TGF-β and IL-8 and are responsible for the degradation of most extracellular matrix proteins during organogenesis, growth and normal tissue turnover. The secreted MMPs maintain the growth factors bioavailable which results in cancer proliferation (20) . Among many factors included in etiopathogenesis of potentially malignant disorders as leukoplakia, MMP-9 plays a main role in tumorigenesis ranging from initiation/promotion to angiogenesis, dissemination, immunological surveillance and metastatic growth.…”