Arsenic enhances matrix metalloproteinase-14 expression in fibroblasts

Masashi Kato1, Khaled Hossain, Machiko Iida

  • 1Unit of Environmental Health Sciences, Department of Biomedical Sciences, College of Life and Health Sciences, Chubu University, Aichi, Japan. katomasa@isc.chubu.ac.jp

Insights

Arsenic exposure increases fibroblast production of active matrix metalloproteinase (MMP)-2 by upregulating MMP-14. This suggests arsenic may promote tumor progression by activating MMP-2, though less effectively than mercury.

Area of Science:

  • Biochemistry
  • Toxicology
  • Cancer Biology

Background:

  • Matrix metalloproteinases (MMPs), particularly MMP-2 and MMP-14, are implicated in tumor progression.
  • Fibroblast-derived MMPs play a crucial role in extracellular matrix remodeling.
  • Understanding the impact of environmental toxins like arsenic on these proteins is vital.

Purpose of the Study:

  • To investigate the effects of arsenic (As) on fibroblast-derived MMP-2 and MMP-14 levels.
  • To elucidate the mechanism by which arsenic influences the active form of MMP-2.
  • To compare the effects of arsenic and mercury (Hg) on MMP-2 activation.

Main Methods:

  • Fibroblast cell cultures were treated with varying concentrations of arsenic (As) and mercury (Hg).
  • Expression levels of MMP-2 and MMP-14 were analyzed.
  • Levels of pro-MMP-2 and active MMP-2 were quantified.

Main Results:

  • Arsenic exposure significantly increased the production of the active form of fibroblast-derived MMP-2.
  • Arsenic treatment elevated MMP-14 expression levels in fibroblasts.
  • Mercury (1000 microM) increased pro-MMP-2 protein, while arsenic did not.
  • MMP-14 acts as an activator of pro-MMP-2.

Conclusions:

  • Arsenic promotes the production of active fibroblast-derived MMP-2 primarily through the upregulation of MMP-14 expression.
  • These findings suggest a potential mechanism for arsenic-induced tumor progression.
  • Arsenic is less potent than mercury in converting pro-MMP-2 to its active form.