Increased plasminogen binding is associated with metastatic breast cancer cells: differential expression of plasminogen binding proteins

Br J Cancer. 1998 May;77(10):1586-97. doi: 10.1038/bjc.1998.261.


Overexpression of urokinase-type plasminogen activator and its receptor correlates with metastatic capacity in breast cancer. In this study we show that the urokinase/urokinase receptor-overexpressing, metastatic human breast cancer cell line MDA-MB-231 (1) bound significantly more cell-surface plasminogen in a lysine-dependent manner and (2) was capable of generating large amounts of plasmin compared with the non-metastatic cell lines MCF-7 and T-47D. In addition, distinct plasminogen binding proteins were detected in the plasma membranes of the cell lines, suggesting heterogeneity of binding proteins. Plasminogen binding was analysed using a combination of dual-colour fluorescence flow cytometry and ligand histochemistry (for comparative and cellular localization of ligand binding), and fluorimetry (for Scatchard analysis). Apart from revealing the greater plasminogen binding capacity of MDA-MB-231 cells, flow cytometry and histochemistry also revealed that, in all three cell lines, non-viable or permeabilized cells bound significantly more plasminogen in a lysine-dependent manner than viable or non-permeabilized cells. Viable MDA-MB-231 cells bound plasminogen with moderate affinity and high capacity (Kd = 1.8 microM, receptor sites per cell 5.0 x 10(7). Our results indicate that differences in cell surface-specific plasminogen binding capacity between cell lines may not be detectable with binding techniques that cannot distinguish between viable and non-viable cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology
  • Cell Membrane / metabolism
  • Fibrinolysin / metabolism
  • Flow Cytometry
  • Humans
  • Neoplasm Invasiveness
  • Neoplasm Metastasis
  • Plasminogen / metabolism*
  • Receptors, Cell Surface / metabolism*
  • Receptors, Urokinase Plasminogen Activator
  • Tumor Cells, Cultured
  • Urokinase-Type Plasminogen Activator / metabolism


  • PLAUR protein, human
  • Receptors, Cell Surface
  • Receptors, Urokinase Plasminogen Activator
  • Plasminogen
  • Fibrinolysin
  • Urokinase-Type Plasminogen Activator