Matrix Metalloproteinases: How Much Can They Do?

Magnus S Ågren,Ulrich Auf Dem Keller

doi:10.3390/ijms21082678

Abstract

Zinc-dependent matrix metalloproteinases (MMPs) belong to metzincins that comprise not only 23 human MMPs but also other metalloproteinases, such as 21 human ADAMs (a disintegrin and metalloproteinase domain) and 19 secreted ADAMTSs (a disintegrin and metalloproteinase thrombospondin domain). The many setbacks from the clinical trials of broad-spectrum MMP inhibitors for cancer indications in the late 1990s emphasized the extreme complexity of the participation of these proteolytic enzymes in biology. This editorial mini-review summarizes the Special Issue, which includes four review articles and 10 original articles that highlight the versatile roles of MMPs, ADAMs, and ADAMTSs, in normal physiology as well as in neoplastic and destructive processes in tissue. In addition, we briefly discuss the unambiguous involvement of MMPs in wound healing.

Highlights

More than half a century ago, Gross and Lapière discovered a true collagenase, which was the first vertebrate matrix metalloproteinase (MMP) responsible for the resorption of the tail in the metamorphosing tadpole [1]
The metzincins, with their third ligand being histidine or aspartate in the active site, comprise the MMP family, which has 23 members in humans [4], and other metalloproteinases, such as adamlysins or reprolysins, including ADAMs and ADAMTSs, consisting of 19 secreted enzymes and at least 7 ADAMTS-like proteins that are devoid of catalytic activity [5,6], astacins, leishmanolysins, serralysins, and snapalysins [2]
Research activities that followed the discovery by Gross and Lapière focused in the beginning on the critical role of these proteinases in extracellular matrix (ECM) remodeling in homeostatic balance and imbalance [7]

Summary

Introduction

More than half a century ago, Gross and Lapière discovered a true collagenase, which was the first vertebrate matrix metalloproteinase (MMP) responsible for the resorption of the tail in the metamorphosing tadpole [1]. These early MMPIs inactivate proteinases unrelated to the disease but necessary for one or more physiological processes [8]; the importance of ADAMs and ADAMTSs was unknown at the time. There is consensus that MMPs, ADAMs, and ADAMTSs function in many cell-signaling pathways, in which they are probably even more important than in ECM remodeling [11,12].

Results

Conclusion