The Role of the Metzincin Superfamily in Prostate Cancer Progression: A Systematic-Like Review

Int J Mol Sci. 2021 Mar 30;22(7):3608. doi: 10.3390/ijms22073608.

Abstract

Prostate cancer remains a leading cause of cancer-related morbidity in men. Potentially important regulators of prostate cancer progression are members of the metzincin superfamily of proteases, principally through their regulation of the extracellular matrix. It is therefore timely to review the role of the metzincin superfamily in prostate cancer and its progression to better understand their involvement in this disease. A systematic-like search strategy was conducted. Articles that investigated the roles of members of the metzincin superfamily and their key regulators in prostate cancer were included. The extracted articles were synthesized and data presented in tabular and narrative forms. Two hundred and five studies met the inclusion criteria. Of these, 138 investigated the role of the Matrix Metalloproteinase (MMP) subgroup, 34 the Membrane-Tethered Matrix Metalloproteinase (MT-MMP) subgroup, 22 the A Disintegrin and Metalloproteinase (ADAM) subgroup, 8 the A Disintegrin and Metalloproteinase with Thrombospondin Motifs (ADAMTS) subgroup and 53 the Tissue Inhibitor of Metalloproteinases (TIMP) family of regulators, noting that several studies investigated multiple family members. There was clear evidence that specific members of the metzincin superfamily are involved in prostate cancer progression, which can be either in a positive or negative manner. However, further understanding of their mechanisms of action and how they may be used as prognostic indicators or molecular targets is required.

Keywords: A Disintegrin and Metalloproteinase; A Disintegrin and Metalloproteinase with Thrombospondin Motifs; Matrix Metalloproteinase; Tissue Inhibitor of Metalloproteinases; metzincin; prostate cancer.

Publication types

  • Systematic Review

MeSH terms

  • ADAM Proteins / metabolism
  • ADAMTS Proteins / metabolism
  • Extracellular Matrix / physiology
  • Humans
  • Male
  • Matrix Metalloproteinases / metabolism
  • Matrix Metalloproteinases, Membrane-Associated / metabolism
  • Metalloproteases / metabolism*
  • Metalloproteases / physiology*
  • Prostate / pathology
  • Prostatic Neoplasms / metabolism*
  • Tissue Inhibitor of Metalloproteinases / metabolism

Substances

  • Tissue Inhibitor of Metalloproteinases
  • Metalloproteases
  • ADAM Proteins
  • ADAMTS Proteins
  • Matrix Metalloproteinases
  • Matrix Metalloproteinases, Membrane-Associated