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Stimulation of cell surface plasminogen activation by membrane-bound melanotransferrin: a key phenomenon for cell
Jonathan Michaud-Levesque1, Michel Demeule, Richard Béliveau
1Laboratoire 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.
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.
Insights
Membrane-bound melanotransferrin (mMTf) acts as a cell surface receptor, enhancing plasminogen binding and activation. This process significantly increases cell migration and invasion, highlighting mMTf
Area of Science:
- Cell Biology
- Biochemistry
- Cancer Research
Background:
- Cell surface plasminogen activation is vital for cell migration and invasion.
- Melanotransferrin (MTf), also known as human melanoma antigen p97, is implicated in cellular processes.
Purpose of the Study:
- To investigate the role of membrane-bound melanotransferrin (mMTf) in cell surface plasminogen binding and activation.
- To determine the impact of mMTf on cell migration, motility, and invasion.
Main Methods:
- Utilized Chinese Hamster Ovary (CHO) cells transfected with MTf cDNA and SK-MeL-28 melanoma cells.
- Assessed plasminogen binding and activation on cell surfaces.
- Evaluated cell motility, migration, and invasion rates.
- Employed monoclonal antibody L235 and soluble MTf (sMTf) to inhibit mMTf function.
Main Results:
- mMTf expression in CHO cells increased cell surface plasminogen binding approximately 2-fold.
- mMTf expression stimulated cell surface plasminogen activation by about 2.5-fold.
- CHO cells expressing mMTf exhibited a 3-fold increase in motility, migration, and invasion.
- Monoclonal antibody L235 and sMTf inhibited mMTf-mediated increases in cell migration and invasion.
Conclusions:
- mMTf functions as a cell surface receptor for plasminogen.
- mMTf plays a key role in regulating plasminogen activation at the cell surface.
- mMTf significantly contributes to cell migration, invasion, and motility, suggesting its involvement in cancer progression.
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