Abstract
The extracellular matrix (ECM) plays an important role in the regulation of the tissue microenvironment and in the maintenance of cellular homeostasis. Several proteins with a proteolytic activity toward several ECM components are involved in the regulation and remodeling of the ECM. Among these, Matrix Metalloproteinases (MMPs) are a class of peptidase able to remodel the ECM by favoring the tumor invasive processes. Of these peptidases, MMP-9 is the most involved in the development of cancer, including that of melanoma. Dysregulations of the MAPKs and PI3K/Akt signaling pathways can lead to an aberrant overexpression of MMP-9. Even ncRNAs are implicated in the aberrant production of MMP-9 protein, as well as other proteins responsible for the activation or inhibition of MMP-9, such as Osteopontin and Tissue Inhibitors of Metalloproteinases. Currently, there are different therapeutic approaches for melanoma, including targeted therapies and immunotherapies. However, no biomarkers are available for the prediction of the therapeutic response. In this context, several studies have tried to understand the diagnostic, prognostic and therapeutic potential of MMP-9 in melanoma patients by performing clinical trials with synthetic MMPs inhibitors. Therefore, MMP-9 may be considered a promising molecule for the management of melanoma patients due to its role as a biomarker and therapeutic target.
Highlights
The extracellular matrix (ECM) plays several roles in the regulation of cellular homeostasis and in the regulation of cell-cell interactions
The role of the Matrix Metalloproteinases (MMPs) family and OPN have been widely described in order to understand their involvement in tumorigenesis, but the actual use of these proteins as biomarkers or therapeutic targets is still far away from happening
The paragraphs discussed above indicate that there is the need for discovering non-invasive biomarkers to assess the progression of melanoma both, during and after the therapy with small molecules, like Dabrafenib or other Mitogen-Activated Protein Kinase (MAPK) inhibitors
Summary
The extracellular matrix (ECM) plays several roles in the regulation of cellular homeostasis and in the regulation of cell-cell interactions. The hyperactivation of MAPKs pathways is associated with the over-expression of the transcription factor ERK that in turn leads to the over-expression of several genes involved in tumor development, including MMPs, TGFβ, and Osteopontin (OPN), whose role in melanoma is fundamental for the tumor invasion and metastatic processes [32,33,34] Starting from these preliminary data on the physiological and pathological role of ECM and MMPs, and taking into account the epidemiological, molecular and mutational data of melanoma, this article aims to review the current knowledge on the involvement of MMPs. Starting from these preliminary data on the physiological and pathological role of ECM and MMPs, and taking into account the epidemiological, molecular and mutational data of melanoma, this article aims to review the current knowledge on the involvement of MMPs It will focus on Matrix Metalloproteinase 9 (MMP-9), in the degradation of ECM and the consequent progression of melanoma, as well as the potential therapeutic implication of both endogenous and exogenous MMP inhibitors for the design of new therapeutic protocols for melanoma patients
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