Could inhibition of metalloproteinases be used to block the process of metastasis?

• Published in: Cell biochemistry and function Vol. 40; no. 6; pp. 600 - 607
• Main Authors: Alba, Jesús, Barcia, Ramiro, Gutiérrez‐Berzal, Javier, Ramos‐Martínez, Juan I.
• Format: Journal Article
• Language: English
• Published: Bognor Regis Wiley Subscription Services, Inc 01.08.2022
• Subjects: Blocking; cancer; Cell migration; Circulatory system; Cytokines; Destabilization; Epithelial cells; epithelial–mesenchymal transition (EMT); Epithelium; Extracellular matrix; extracellular matrix (ECM); Matrilysin; Matrix metalloproteinase; Matrix metalloproteinases; matrix metalloproteinases (MMPs); Mesenchyme; Metastases; Metastasis; Stroma; Tumor cells; Tumors
• ISSN: 0263-6484; 1099-0844; 1099-0844
• DOI: 10.1002/cbf.3730

Metastasis is a multisequential process that allows tumor cells to migrate to tissues distant from the primary tumor. Only a small number of cells escape from the primary tumor; however, the metastases generated are responsible for more than 90% of cancer deaths. Many metastatic processes initially require the total or partial start‐up of a program for the transformation of tumor epithelial cells into mesenchymal cells (EMT). The launching of the EMT program is stimulated by cytokines and other elements produced by the diverse types of cells composing the tumor stroma. In parallel, a process of destabilization of the extracellular matrix (ECM) takes place by means of the synthesis of proteases of the matrix metalloproteinases (MMPs) family. EMC degradation allows the exportation of some tumor cells as mesenchymal cells to the circulatory system and their subsequent implantation in a tissue distant from the primary tumor. The blocking of these both processes appears as a hypothetical stop point in the metastatic mechanism. The present review deals with the different options to achieve the inhibition of MMPs, focusing on MMP7 as a target given its involvement in the metastatic processes of a wide variety of tumors. Significance statement The simultaneous implantation of the epithelial–mesenchymal program and the synthesis and activation of matrix metalloproteinases during the first phases of the metastasis process is known. The inhibition of proteases could constitute a possible blockage of the process. The review describes the evolution of the different inhibition mechanisms that could inform applicable therapeutic mechanisms for the paralysis of the metastatic process.