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Neutrophil activator of matrix metalloproteinase-2 (NAM)

Ellen E Rollo1, Michelle Hymowitz, Cathleen E Schmidt

  • 1Departments of Research and Medicine, Veterans Affairs Medical Center, Mail Code 151, Northport, NY, 11768, USA.

Clinical & Experimental Metastasis
|November 7, 2006
PubMed

Insights

Researchers discovered neutrophil activator of matrix metalloproteinases (NAM), a novel factor secreted by neutrophils. NAM activates proMMP-2, potentially playing a role in cancer dissemination.

Area of Science:

  • Biochemistry
  • Cell Biology
  • Oncology

Background:

  • Neutrophils are key immune cells with diverse functions.
  • Matrix metalloproteinases (MMPs) are crucial for tissue remodeling and implicated in cancer progression.
  • Activation of proMMP-2 is a critical step in MMP-mediated processes.

Purpose of the Study:

  • To isolate and characterize a novel neutrophil-secreted factor involved in MMP activation.
  • To investigate the role of this factor in the activation of proMMP-2.
  • To explore the potential involvement of this factor in cancer dissemination.

Main Methods:

  • Isolation of neutrophil activator of matrix metalloproteinases (NAM) from neutrophil-conditioned media using gelatin-Sepharose chromatography and differential membrane filtration.
  • Assessing NAM activity by exposing human umbilical vein endothelial cells (HUVEC) and HT1080 cells to NAM, followed by gelatin zymography.
  • Investigating the effect of various inhibitors (TIMP-2, CT1746, BB94) on NAM-induced proMMP-2 activation and TIMP-2 binding.
  • Analyzing MT1-MMP protein and mRNA expression following NAM treatment.

Main Results:

  • A novel soluble factor, NAM, was isolated from unstimulated human neutrophils.
  • NAM directly activates cell-secreted proMMP-2 within one hour.
  • NAM-induced proMMP-2 activation and increased TIMP-2 binding were inhibited by specific MMP inhibitors.
  • NAM treatment led to time-dependent increases in MT1-MMP protein and mRNA levels.

Conclusions:

  • Neutrophil activator of matrix metalloproteinases (NAM) is a novel neutrophil-secreted factor that activates proMMP-2.
  • NAM influences TIMP-2 binding and MT1-MMP expression.
  • These findings suggest a potential role for NAM in cancer cell dissemination and invasion.

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