Abstract
Metalloproteinases (MMPs) have an important role in tissue remodeling and have been shown to have an effect on tumor progression, invasion, metastasis formation, and apoptosis in several tumors, including mesothelioma. Mesothelioma is a rare tumor arising from pleura and peritoneum and is frequently associated with asbestos exposure. We have performed a systematic search of PubMed.gov and ClinicalTrials.gov databases to retrieve and review three groups of studies: studies of MMPs expression in tumor tissue or body fluids in patients with mesothelioma, studies of MMPs genetic variability, and studies of MMPs as potential novel drug targets in mesothelioma. Several studies of MMPs in mesothelioma tissues reported a link between higher expression levels of commonly studied MMPs and clinical parameters, such as overall survival. Fewer studies have investigated genetic variability of MMP genes. Nevertheless, these studies suggested that certain genetic variants in MMP genes can have either protective or tumor-promoting effects on mesothelioma patients. MMPs have been also reported as novel drug targets, but so far no clinical trials of MMP inhibitors are registered in mesothelioma. In conclusion, MMPs play an important role in mesothelioma, but further studies are needed to elucidate the potentials of MMPs as biomarkers and drug targets in mesothelioma.
Highlights
Matrix metalloproteinases (MMPs) have been reported as novel drug targets, but so far no clinical trials of MMP inhibitors are registered in mesothelioma
MMPs play an important role in mesothelioma, but further studies are needed to elucidate the potentials of MMPs as biomarkers and drug targets in mesothelioma
MMP expression and genetic variation may have an important role in mesothelioma as prognostic biomarkers and as potential treatment target
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. MMP14 is involved in activation of the proMMP2 and plays a role in activation of mechanisms of tissue matrix remodeling, tumor angiogenesis, cell signaling, migration, and inflammation [12]. Someloss other studies investigating MMPs in mesothelioma focused on the basic roles of MMPs in tumor invasion progression [18,19]. MT1-MMP by RNA interference (RNAi) to assess the role of MT1-MMP in the invasive clinical specimen of a patient with mesothelioma They have silenced the expression o activity of mesothelioma cells. They concluded that there is a biological role for MSLN as a factor-promoting tumor invasion and MMP-9 expression in MSLN-expressing mesothelioma tissue [21]. Recent studies have focused on elucidating genetic mechanisms that control MMPs expression in mesothelioma as these genetic mechanisms may be potential future targets for therapies
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