Requirement for Specific Proteases in Cancer Cell Intravasation as Revealed by a Novel Semiquantitative PCR-based Assay

Cell. 1998 Aug 7;94(3):353-62. doi: 10.1016/s0092-8674(00)81478-6.

Abstract

Proteases are crucial for cancer metastasis, but due to lack of assays, their role in intravasation has not yet been tested. We have developed a human Alu sequence PCR-based assay to quantitate intravasated cells in an in vivo model. We demonstrated that metalloproteinases (MMPs), and most likely MMP-9, are required for intravasation by showing that marimastat, an inhibitor of MMPs, reduced intravasation by more than 90%, and that only tumor cell lines expressing MMP-9 intravasated. Cells with low surface urokinase plasminogen activator (uPA) and uPA receptor (uPAR) were also incapable of intravasation, despite the presence of high levels of MMP-9. We concluded that breaching of the vascular wall is a rate-limiting step for intravasation, and consequently for metastasis, and that cooperation between uPA/uPAR and MMP-9 is required to complete this step.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Allantois
  • Animals
  • Cell Membrane / enzymology
  • Cell Membrane / pathology
  • Cell Transformation, Neoplastic / pathology
  • Chick Embryo
  • Chorion
  • Endopeptidases / physiology*
  • Female
  • Humans
  • Hydrolysis
  • Male
  • Neoplasm Invasiveness / genetics
  • Neoplasm Invasiveness / pathology*
  • Neoplasm Metastasis / genetics
  • Neoplasm Metastasis / pathology*
  • Polymerase Chain Reaction / methods*
  • Repetitive Sequences, Nucleic Acid / genetics
  • Sensitivity and Specificity
  • Tumor Cells, Cultured
  • Vascular Neoplasms / enzymology
  • Vascular Neoplasms / pathology

Substances

  • Endopeptidases