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

Journal Article


Abstract


  • 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 (K(d) = 1.8 μM1 receptor sites per cell 5.0 x 107. 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 Date


  • 1998

Citation


  • Ranson, M., Andronicos, N. M., O'Mullane, M. J., & Baker, M. S. (1998). Increased plasminogen binding is associated with metastatic breast cancer cells: Differential expression of plasminogen binding proteins. British Journal of Cancer, 77(10), 1586-1597. doi:10.1038/bjc.1998.261

Scopus Eid


  • 2-s2.0-0031972273

Start Page


  • 1586

End Page


  • 1597

Volume


  • 77

Issue


  • 10

Abstract


  • 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 (K(d) = 1.8 μM1 receptor sites per cell 5.0 x 107. 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 Date


  • 1998

Citation


  • Ranson, M., Andronicos, N. M., O'Mullane, M. J., & Baker, M. S. (1998). Increased plasminogen binding is associated with metastatic breast cancer cells: Differential expression of plasminogen binding proteins. British Journal of Cancer, 77(10), 1586-1597. doi:10.1038/bjc.1998.261

Scopus Eid


  • 2-s2.0-0031972273

Start Page


  • 1586

End Page


  • 1597

Volume


  • 77

Issue


  • 10