Staphylococcal SSL5 Binding to Human Leukemia Cells Inhibits Cell Adhesion to Endothelial Cells and Platelets
Bacterial proteins provide promising tools for novel anticancer therapies. Staphylococcal superantigen-like 5 (SSL5) was recently described to bind P-selectin glycoprotein ligand-1 (PSGL-1) on leukocytes and to inhibit neutrophil rolling on a P-selectin surface. As leukocytes and tumor cells share m...
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| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2010-01-01
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| Series: | Cellular Oncology |
| Online Access: | http://dx.doi.org/10.3233/CLO-2009-0486 |
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| _version_ | 1832566810455572480 |
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| author | Annemiek M. E. Walenkamp Jovanka Bestebroer Ingrid G. J. Boer Roeline Kruizinga Henk M. Verheul Jos A. G. van Strijp Carla J. C. de Haas |
| author_facet | Annemiek M. E. Walenkamp Jovanka Bestebroer Ingrid G. J. Boer Roeline Kruizinga Henk M. Verheul Jos A. G. van Strijp Carla J. C. de Haas |
| author_sort | Annemiek M. E. Walenkamp |
| collection | DOAJ |
| description | Bacterial proteins provide promising tools for novel anticancer therapies. Staphylococcal superantigen-like 5 (SSL5) was recently described to bind P-selectin glycoprotein ligand-1 (PSGL-1) on leukocytes and to inhibit neutrophil rolling on a P-selectin surface. As leukocytes and tumor cells share many characteristics in migration and dissemination, we explored the potential of SSL5 as an antagonist of malignant cell behavior. Previously, it was demonstrated that rolling of human HL-60 leukemia cells on activated endothelial cells was mediated by P-selectin. In this study, we show that SSL5 targets HL-60 cells. Binding of SSL5 was rapid and without observed toxicity. Competition of SSL5 with the binding of three anti-PSGL-1 antibodies and P-selectin to HL-60 cells identified PSGL-1 as the ligand on HL-60 cells. Presence of sialyl Lewis x epitopes on PSGL-1 was crucial for its interaction with SSL5. Importantly, SSL5 not only inhibited the interaction of HL-60 cells with activated endothelial cells but also with platelets, which both play an important role in growth and metastasis of cancers. These data support the concept that SSL5 could be a lead in the search for novel strategies against hematological malignancies. |
| format | Article |
| id | doaj-art-3c1f01beeb614de3bc89c9e5571dfd8b |
| institution | Kabale University |
| issn | 1570-5870 1875-8606 |
| language | English |
| publishDate | 2010-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Cellular Oncology |
| spelling | doaj-art-3c1f01beeb614de3bc89c9e5571dfd8b2025-02-03T01:02:59ZengWileyCellular Oncology1570-58701875-86062010-01-01321-211010.3233/CLO-2009-0486Staphylococcal SSL5 Binding to Human Leukemia Cells Inhibits Cell Adhesion to Endothelial Cells and PlateletsAnnemiek M. E. Walenkamp0Jovanka Bestebroer1Ingrid G. J. Boer2Roeline Kruizinga3Henk M. Verheul4Jos A. G. van Strijp5Carla J. C. de Haas6Department of Medical Oncology, University Medical Center Groningen, Groningen, The NetherlandsMedical Microbiology, University Medical Center Utrecht, Utrecht, The NetherlandsMedical Microbiology, University Medical Center Utrecht, Utrecht, The NetherlandsDepartment of Medical Oncology, University Medical Center Groningen, Groningen, The NetherlandsDepartment of Medical Oncology, VU Medical Center, Amsterdam, The NetherlandsMedical Microbiology, University Medical Center Utrecht, Utrecht, The NetherlandsMedical Microbiology, University Medical Center Utrecht, Utrecht, The NetherlandsBacterial proteins provide promising tools for novel anticancer therapies. Staphylococcal superantigen-like 5 (SSL5) was recently described to bind P-selectin glycoprotein ligand-1 (PSGL-1) on leukocytes and to inhibit neutrophil rolling on a P-selectin surface. As leukocytes and tumor cells share many characteristics in migration and dissemination, we explored the potential of SSL5 as an antagonist of malignant cell behavior. Previously, it was demonstrated that rolling of human HL-60 leukemia cells on activated endothelial cells was mediated by P-selectin. In this study, we show that SSL5 targets HL-60 cells. Binding of SSL5 was rapid and without observed toxicity. Competition of SSL5 with the binding of three anti-PSGL-1 antibodies and P-selectin to HL-60 cells identified PSGL-1 as the ligand on HL-60 cells. Presence of sialyl Lewis x epitopes on PSGL-1 was crucial for its interaction with SSL5. Importantly, SSL5 not only inhibited the interaction of HL-60 cells with activated endothelial cells but also with platelets, which both play an important role in growth and metastasis of cancers. These data support the concept that SSL5 could be a lead in the search for novel strategies against hematological malignancies.http://dx.doi.org/10.3233/CLO-2009-0486 |
| spellingShingle | Annemiek M. E. Walenkamp Jovanka Bestebroer Ingrid G. J. Boer Roeline Kruizinga Henk M. Verheul Jos A. G. van Strijp Carla J. C. de Haas Staphylococcal SSL5 Binding to Human Leukemia Cells Inhibits Cell Adhesion to Endothelial Cells and Platelets Cellular Oncology |
| title | Staphylococcal SSL5 Binding to Human Leukemia Cells Inhibits Cell Adhesion to Endothelial Cells and Platelets |
| title_full | Staphylococcal SSL5 Binding to Human Leukemia Cells Inhibits Cell Adhesion to Endothelial Cells and Platelets |
| title_fullStr | Staphylococcal SSL5 Binding to Human Leukemia Cells Inhibits Cell Adhesion to Endothelial Cells and Platelets |
| title_full_unstemmed | Staphylococcal SSL5 Binding to Human Leukemia Cells Inhibits Cell Adhesion to Endothelial Cells and Platelets |
| title_short | Staphylococcal SSL5 Binding to Human Leukemia Cells Inhibits Cell Adhesion to Endothelial Cells and Platelets |
| title_sort | staphylococcal ssl5 binding to human leukemia cells inhibits cell adhesion to endothelial cells and platelets |
| url | http://dx.doi.org/10.3233/CLO-2009-0486 |
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