| Autor: |
Goerge T; University of Münster, Department of Dermatology, Münster, Germany. Tobias.Goerge@ukmuenster.de, Kleinerüschkamp F, Barg A, Schnaeker EM, Huck V, Schneider MF, Steinhoff M, Schneider SW |
| Jazyk: |
angličtina |
| Zdroj: |
Thrombosis and haemostasis [Thromb Haemost] 2007 Aug; Vol. 98 (2), pp. 283-6. |
| Abstrakt: |
Neoplastic diseases are often associated with thromboembolic events, however the precise mechanism underlying this observation is a matter of ongoing investigation. It is known that matrixmetalloproteinase-1 (MMP-1) canonically activates the thrombin receptor (PAR-1) and we recently reported that highly metastatic tumor cells of melanoma and colon cancer are secreting matrixmetalloproteinase-1. This tumor-derived MMP1 was shown to be a major activator of endothelial PAR-1, thus leading to endothelial cell activation. As tumor-induced thrombosis is a characteristic of metastazing tumors, we investigated whether tumor-derived supernatant (TUSN) from melanoma and colon cancer may induce adhesion of circulating platelets, an initial step in thrombus formation. A time-course study revealed that TU-SN induces a rapid secretion of von Willebrand factor (VWF) within minutes. Using a novel microfluidic device we analyzed platelet-endothelial interactions in a closed circuit. Immunofluorescence imaging showed that TU-SN rapidly induces platelet-string formation via secreted VWF. We demonstrated that tumor-derived supernatant is a potent agonist inducing platelet adhesion under flow conditions. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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