Stimulation of cell surface plasminogen activation by membrane-bound melanotransferrin: a key phenomenon for cell invasion.
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.
Michaud-Levesque
Jonathan
J
Laboratoire de Médecine Moléculaire, Service d'Hémato-Oncologie, Hôpital Ste-Justine-Université du Québec à Montréal (UQAM), C.P. 8888, Succursale Centre-ville, Montréal, Québec, Canada H3C 3P8.
Demeule
Michel
M
Béliveau
Richard
R
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000951:Antigens, Neoplasm; D016466:CHO Cells; D002462:Cell Membrane / Q000378:metabolism*; D002465:Cell Movement / Q000502:physiology; D006224:Cricetinae; D018076:DNA, Complementary / Q000235:genetics; D006801:Humans; D058950:Melanoma-Specific Antigens; D009361:Neoplasm Invasiveness / Q000503:physiopathology*; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D010958:Plasminogen / Q000378:metabolism*; D010960:Plasminogen Activators / Q000378:metabolism; D011485:Protein Binding / Q000502:physiology; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D055293:Receptors, Urokinase Plasminogen Activator; D014162:Transfection; D015854:Up-Regulation / Q000502:physiology
D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D018076:DNA, Complementary; D058950:Melanoma-Specific Antigens; D009363:Neoplasm Proteins; C524898:PLAUR protein, human; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator; D010958:Plasminogen; D010960:Plasminogen Activators