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Secretion of active membrane type 1 matrix metalloproteinase (MMP-14) into extracellular space in microvesicular

Juha Hakulinen1, Lotta Sankkila, Nami Sugiyama

  • 1Department of Pathology, Haartman Institute, University of Helsinki, and Helsinki University Hospital, Helsinki, Finland. juha.hakulinen@helsinki.fi

Journal of Cellular Biochemistry
|September 20, 2008
PubMed

Insights

Membrane type 1 matrix metalloproteinase (MT1-MMP) is secreted in exosomes, enabling cancer cells to degrade extracellular matrix. This exosomal MT1-MMP is functionally active, suggesting a novel mechanism for cancer cell invasion.

Area of Science:

  • Biochemistry
  • Cell Biology
  • Cancer Research

Background:

  • Membrane type 1 matrix metalloproteinase (MT1-MMP) degrades extracellular matrix (ECM), crucial for tissue homeostasis and cell invasion.
  • MT1-MMP, like other type I membrane proteins, undergoes endocytosis and recycling.
  • Late endosomes are involved in exosome biogenesis and secretion of plasma membrane proteins.

Purpose of the Study:

  • To investigate whether MT1-MMP is secreted via exosomes.
  • To determine if exosomal MT1-MMP retains its enzymatic activity.

Main Methods:

  • Cultured human fibrosarcoma (HT-1080) and melanoma (G361) cells were used.
  • Exosomes were isolated and characterized using electron microscopy and exosomal markers (CD9, TSG101).
  • The presence of MT1-MMP and beta1-integrin (CD29) in exosomes was analyzed.

Main Results:

  • Both full-length (60 kDa) and processed (43 kDa) MT1-MMP were detected in secreted exosomes.
  • Exosomes contained exosomal markers (CD9, TSG101) and beta1-integrin (CD29).
  • Exosomal MT1-MMP demonstrated functional activity by activating pro-MMP-2 and degrading collagen and gelatin.

Conclusions:

  • MT1-MMP is targeted to exosomes for extracellular release.
  • Exosomal MT1-MMP is functionally active, contributing to ECM degradation.
  • This represents a novel mechanism for cancer cells to secrete metalloproteolytic activity.

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