The Many Facets of Metzincins and Their Endogenous Inhibitors: Perspectives on Ovarian Cancer Progression

Int J Mol Sci. 2018 Feb 2;19(2):450. doi: 10.3390/ijms19020450.

Abstract

Approximately sixty per cent of ovarian cancer patients die within the first five years of diagnosis due to recurrence associated with chemoresistance. The metzincin family of metalloproteinases is enzymes involved in matrix remodeling in response to normal physiological changes and diseased states. Recently, there has been a mounting awareness of these proteinases and their endogenous inhibitors, the tissue inhibitors of metalloproteinases (TIMPs), as superb modulators of cellular communication and signaling regulating key biological processes in cancer progression. This review investigates the role of metzincins and their inhibitors in ovarian cancer. We propose that understanding the metzincins and TIMP biology in ovarian cancer may provide valuable insights in combating ovarian cancer progression and chemoresistance-mediated recurrence in patients.

Keywords: ADAM proteases with thrombospondin motifs (ADAMTS); TIMPs; disintegrin and metalloproteinases (ADAMs); matrix metalloproteinases (MMPs); metastasis; metzincins; ovarian cancer.

Publication types

  • Review

MeSH terms

  • ADAMTS Proteins / genetics*
  • ADAMTS Proteins / metabolism
  • Antineoplastic Agents / pharmacology
  • Disease Progression
  • Drug Resistance, Neoplasm / genetics
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Matrix Metalloproteinases / genetics*
  • Matrix Metalloproteinases / metabolism
  • Neoplasm Recurrence, Local / drug therapy
  • Neoplasm Recurrence, Local / genetics*
  • Neoplasm Recurrence, Local / mortality
  • Neoplasm Recurrence, Local / pathology
  • Ovarian Neoplasms / drug therapy
  • Ovarian Neoplasms / genetics*
  • Ovarian Neoplasms / mortality
  • Ovarian Neoplasms / pathology
  • Ovary / drug effects
  • Ovary / metabolism
  • Ovary / pathology
  • Signal Transduction
  • Survival Analysis
  • Tissue Inhibitor of Metalloproteinases / genetics*
  • Tissue Inhibitor of Metalloproteinases / metabolism

Substances

  • Antineoplastic Agents
  • Tissue Inhibitor of Metalloproteinases
  • ADAMTS Proteins
  • Matrix Metalloproteinases