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Functional effect of contortrostatin, a snake venom disintegrin, on human glioma cell invasion in vitro

Stephanie Schmitmeier1, Francis S Markland, Matthew R Ritter

  • 1Department of Biochemistry and Molecular Biology, University of Southern California, Keck School of Medicine and Norris Comprehensive Cancer Center, 1200 N. State St. #5046, Los Angeles, CA 90033, USA.

Cell Communication & Adhesion
|July 26, 2003
PubMed

Insights

Contortrostatin (CN), a snake venom disintegrin, effectively inhibits glioma cell invasion by impairing cell motility, not adhesion. This suggests CN is a versatile anti-invasion agent targeting multiple integrins.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Cancer metastasis involves complex cellular actions like ECM adhesion, ECM breakdown, and cell locomotion.
  • Contortrostatin (CN), a snake venom disintegrin, previously showed potential in blocking glioblastoma cell adhesion and invasion.
  • The precise mechanism and stage of invasion inhibited by CN remained unclear.

Purpose of the Study:

  • To elucidate the mechanism by which Contortrostatin (CN) inhibits glioma cell invasion.
  • To determine at which step of the invasion process CN exerts its inhibitory effect.
  • To investigate the versatility of CN in targeting different glioma cell lines and integrins.

Main Methods:

  • Assessed CN's effect on glioma cell invasion through Matrigel.
  • Evaluated CN's impact on cell adhesion to various extracellular matrix components (laminin, collagen, vitronectin, fibronectin).
  • Investigated the role of matrix metalloproteinases (MMP) and plasminogen activator (PA)/plasmin systems.
  • Analyzed CN's effect on active cell locomotion and interaction with specific integrins (alphav beta3, alphav beta5, alpha5beta1).

Main Results:

  • CN decreased glioma cell invasion through Matrigel without affecting cell adhesion or viability.
  • CN blocked adhesion to vitronectin and fibronectin in alphav beta3-positive cells but not in negative cells.
  • CN did not involve MMP or PA/plasmin systems; instead, it inhibited active cell locomotion.
  • CN demonstrated versatility by inhibiting invasion through interaction with multiple integrins (alphav beta3, alphav beta5, alpha5beta1).

Conclusions:

  • CN-mediated inhibition of glioma cell invasion is primarily due to impaired cell motility.
  • CN acts as a direct inhibitor of cell locomotion, offering a novel therapeutic strategy.
  • CN's ability to interact with various integrins highlights its potential as a versatile anti-invasion agent for gliomas.

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