Stimulation of cell surface plasminogen activation by membrane-bound melanotransferrin: a key phenomenon for cell invasion

Exp Cell Res. 2005 Aug 15;308(2):479-90. doi: 10.1016/j.yexcr.2005.05.004.

Abstract

The activation of plasminogen at the cell surface is a crucial step in cell migration and invasion. In the present study, the effect of membrane-bound melanotransferrin (mMTf), also known as human melanoma antigen p97, on cell surface plasminogen binding and activation was investigated by using Chinese Hamster Ovary (CHO) cells transfected with full-length melanotransferrin (MTf) cDNA and SK-MeL-28 melanoma cells. The expression of mMTf in CHO increased cell surface plasminogen binding by about 2-fold. In addition, application of the monoclonal antibody L235 against MTf as well as truncated, soluble MTf (sMTf) abolished plasminogen binding to MTf-transfected and SK-MeL-28 cells, indicating that mMTf is a potential cell surface plasminogen receptor. Moreover, mMTf expression in CHO cells stimulates plasminogen activation at the cell surface by about 2.5-fold. In addition to the induced binding and activation of plasminogen, cell motility, migration and invasion were about 3-fold higher in CHO cells expressing mMTf. Both monoclonal antibody L235 and truncated sMTf inhibited mMTf-stimulated CHO cell motility, migration and invasion. Overall, our results indicate a key role for mMTf in cell surface plasminogen binding and in activation processes involved during cell migration and invasion.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / pharmacology
  • Antigens, Neoplasm
  • CHO Cells
  • Cell Membrane / metabolism*
  • Cell Movement / physiology
  • Cricetinae
  • DNA, Complementary / genetics
  • Humans
  • Melanoma-Specific Antigens
  • Neoplasm Invasiveness / physiopathology*
  • Neoplasm Proteins / antagonists & inhibitors
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism*
  • Plasminogen / metabolism*
  • Plasminogen Activators / metabolism
  • Protein Binding / physiology
  • Receptors, Cell Surface / genetics
  • Receptors, Cell Surface / metabolism*
  • Receptors, Urokinase Plasminogen Activator
  • Transfection
  • Up-Regulation / physiology

Substances

  • Antibodies, Monoclonal
  • Antigens, Neoplasm
  • DNA, Complementary
  • Melanoma-Specific Antigens
  • Neoplasm Proteins
  • PLAUR protein, human
  • Receptors, Cell Surface
  • Receptors, Urokinase Plasminogen Activator
  • Plasminogen
  • Plasminogen Activators