Department of Biomedical and Biotechnological Sciences, University of Catania, 95123 Catania, Italy.
Research Center for Prevention, Diagnosis and Treatment of Cancer, University of Catania, 95123 Catania, Italy.
Cells. 2020 May 7;9(5):1151. doi: 10.3390/cells9051151.
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 . 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.
细胞外基质 (ECM) 在调节组织微环境和维持细胞内稳态方面起着重要作用。几种具有多种 ECM 成分水解活性的蛋白质参与 ECM 的调节和重塑。其中，基质金属蛋白酶 (MMPs) 是一类能够通过促进肿瘤侵袭过程来重塑 ECM 的肽酶。在这些肽酶中，MMP-9 最参与癌症的发展，包括黑色素瘤。MAPKs 和 PI3K/Akt 信号通路的失调可导致 MMP-9 的异常过表达。甚至非编码 RNA 也与 MMP-9 蛋白以及其他负责 MMP-9 激活或抑制的蛋白质（如骨桥蛋白和金属蛋白酶组织抑制剂）的异常产生有关。目前，有多种针对黑色素瘤的治疗方法，包括靶向治疗和免疫疗法。然而，目前尚无预测治疗反应的生物标志物。在这种情况下，一些研究通过使用合成 MMPs 抑制剂进行临床试验，试图了解 MMP-9 在黑色素瘤患者中的诊断、预后和治疗潜力。因此，MMP-9 由于其作为生物标志物和治疗靶点的作用，可能被认为是黑色素瘤患者管理的有前途的分子。
