Recent advances in understanding the roles of matrix metalloproteinases in tumour invasion and metastasis

J Pathol. 2019 Apr;247(5):629-640. doi: 10.1002/path.5225. Epub 2019 Feb 15.

Abstract

This review aims to provide an overview of recent developments regarding the roles of MMPs in tumour invasion and metastasis. Much of the mortality burden belonging to cancer relates to its ability to invade adjacent tissue and form metastases at distant sites. This would not be possible without remodelling of the ECM, a process which is enabled by the functions of MMPs. Recent studies provide a better understanding of the importance of the biophysical nature of the ECM, how this influences cancer cell motility, and how MMPs act to modify matrix stiffness. The regulation of MMPs and the role of immune cell generated MMPs has also become better understood. All of this provides a framework for the therapeutic targeting of MMPs and recent advances in the development of selective MMPs inhibitors are also reviewed. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Keywords: ECM; MMPs; metastasis; microenvironment; protease; tumour invasion; tumour progression.

Publication types

  • Review

MeSH terms

  • Antigens, CD / physiology
  • Extracellular Matrix / pathology
  • Humans
  • Immune System / physiology
  • Matrix Metalloproteinase Inhibitors / therapeutic use
  • Matrix Metalloproteinases / physiology*
  • Neoplasm Invasiveness
  • Neoplasm Metastasis
  • Neoplasms / immunology
  • Neoplasms / pathology*
  • Receptors, G-Protein-Coupled / physiology
  • Sialyltransferases / physiology
  • Terminology as Topic
  • Thrombospondins / physiology
  • Transforming Growth Factor beta / physiology
  • beta-D-Galactoside alpha 2-6-Sialyltransferase

Substances

  • ADGRE5 protein, human
  • Antigens, CD
  • Matrix Metalloproteinase Inhibitors
  • Receptors, G-Protein-Coupled
  • Thrombospondins
  • Transforming Growth Factor beta
  • thrombospondin 2
  • Sialyltransferases
  • Matrix Metalloproteinases
  • beta-D-Galactoside alpha 2-6-Sialyltransferase