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Pericellular activation of proMMP-7 (promatrilysin-1) through interaction with CD151

Takayuki Shiomi1, Isao Inoki, Fumio Kataoka

  • 1Department of Pathology, School of Medicine, Keio University, Tokyo, Japan.

Laboratory Investigation; a Journal of Technical Methods and Pathology
|October 4, 2005
PubMed

Insights

Matrix metalloproteinase-7 (MMP-7) binds to CD151 on cell membranes, facilitating its activation and pericellular proteolysis. This interaction is crucial for cancer invasion and metastasis, offering potential therapeutic targets.

Area of Science:

  • Biochemistry
  • Cell Biology
  • Oncology

Background:

  • Matrix metalloproteinase-7 (MMP-7), also known as matrilysin-1, is a secreted enzyme crucial for extracellular matrix (ECM) degradation.
  • ProMMP-7, the inactive precursor, requires activation to exert its proteolytic functions.
  • Understanding proMMP-7 activation mechanisms is vital for comprehending its role in physiological and pathological processes, particularly cancer.

Purpose of the Study:

  • To identify proteins that bind to and mediate the activation of proMMP-7.
  • To elucidate the interaction between proMMP-7 and its binding partners at the molecular and cellular levels.
  • To investigate the role of this interaction in cancer progression, specifically in lung adenocarcinoma.

Main Methods:

  • Yeast two-hybrid screening to identify proMMP-7 binding proteins.
  • Immunoprecipitation to confirm complex formation between proMMP-7 and candidate proteins.
  • Deletion mutant analysis to map the interaction domains.
  • Cell-based binding assays and confocal microscopy to visualize colocalization.
  • In situ zymography to assess enzymatic activity.
  • Analysis of human lung adenocarcinoma tissues.

Main Results:

  • CD151, a transmembrane 4 superfamily member, was identified as a proMMP-7 binding protein.
  • ProMMP-7 forms a complex with CD151 on the cell membrane, involving the propeptide of MMP-7 and the extracellular loop of CD151.
  • ProMMP-7 colocalizes with CD151 on the cell surface, and this interaction leads to pericellular MMP-7 activation.
  • MMP-7 and CD151 colocalize in human lung adenocarcinoma tissues, where metalloproteinase activity is observed and can be inhibited by specific antibodies.

Conclusions:

  • CD151 acts as a cell surface receptor that captures and facilitates the activation of proMMP-7.
  • This CD151-mediated pericellular activation mechanism of MMP-7 is analogous to the MT1-MMP/MMP-2 system.
  • The MMP-7/CD151 interaction plays a significant role in cancer invasion and metastasis, representing a potential therapeutic target.

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