Plasmin releases the anti-tumor peptide from the NC1 domain of collagen XIX

Jean-Baptiste Oudart1,2, Sylvie Brassart-Pasco1, Alexia Vautrin1

  • 1Université de Reims Champagne-Ardenne, CNRS UMR 7369 (Matrice Extracellulaire et Dynamique Cellulaire, MEDyC), Reims, France.

Oncotarget
|February 11, 2015
PubMed

Insights

Collagen XIX releases an anti-tumor fragment via plasmin, inhibiting tumor cell migration and growth. This suggests a natural defense mechanism against cancer invasion.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Cancer Research

Background:

  • Tumor cells degrade the extracellular matrix during invasion.
  • Basement membrane degradation yields peptides with anti-tumor properties.
  • Type XIX collagen (COL19) is a basement membrane component.

Purpose of the Study:

  • To investigate the interaction between plasmin and collagen XIX.
  • To characterize the anti-tumor activity of collagen XIX fragments.
  • To explore the structural basis of collagen XIX's anti-tumor effects.

Main Methods:

  • Plasmin digestion of collagen XIX.
  • Analysis of released fragments for anti-tumor activity.
  • Molecular modeling of collagen XIX domains and fragments.

Main Results:

  • Plasmin releases a fragment (F4) from collagen XIX's NC1(XIX) domain.
  • The released fragment F4 retains anti-tumor activity, inhibiting tumor cell migration and growth.
  • Molecular modeling revealed a conserved β-turn conformation in NC1(XIX) and F4, suggesting conformation-dependent activity.

Conclusions:

  • Collagen XIX is a novel substrate for plasmin.
  • Plasmin-mediated release of collagen XIX fragments represents a potential endogenous anti-tumor defense mechanism.
  • The anti-tumor activity of collagen XIX is conformation-dependent.

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