Molecular mechanisms of hematogenous tumor - metastasis

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Constantin_Adams_Dissertation.pdf03.12.2007 10:57:332,65 MB
The present manuscript demonstrates that B16F10 melanoma cells activate the enzyme acid sphingomyelinase in thrombocytes via the surface molecule P-selectin, by which ceramide is released. Metastasis of tumor cells in the lung is decreased by up to 95% by genetic deficiency of P-selectin molecule or deficiency of acid sphingomyelinase. After activation of wild type thrombocytes by B16F10 melanoma cells there is a rapid increase in acid sphingomyelinase activity and ceramide production as compared to acid sphingomyelinase-deficient thrombocytes or P-selectin-deficient thrombocytes. A lack of interaction of B16F10 melanoma cells and thrombocytes was excluded by activation of PLCĪ³, JNK and MAP kinase, indicating that these signaling events are stimulated in both, wild-type and P-selectin-deficient platelets, proving that B16F10 melanoma cells interact with and activate P-selectin-deficient thrombocytes. The molecular mechanisms of tumor metastasis are currently fairly incomplete, though metastasis plays a crucial clinical role in cancer patients. Acid sphingomyelinase is iidentified as a novel target molecule for the inhibition of tumor metastasis. In order to pharmacologically inhibit the thrombocytic P-selectin system, an intravenous injection of fucoidan showed a decrease of tumor metastasis of B16F10 melanoma cells by approximately 75%. This indicates that tumor metastasis can be blocked pharmacologically, which is of great clinical interest.
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Dokumententyp:
Wissenschaftliche Abschlussarbeiten » Dissertation
Fakultät / Institut:
ehem. Fakultät für Biologie und Geografie
Dewey Dezimal-Klassifikation:
500 Naturwissenschaften und Mathematik » 570 Biowissenschaften; Biologie
Beitragende:
Prof. Dr. med. Gulbins, Erich [Betreuer(in), Doktorvater]
Prof. Dr. Ehrmann, Michael [Gutachter(in), Rezensent(in)]
Sprache:
Englisch
Kollektion / Status:
Dissertationen / Dokument veröffentlicht
Datum der Promotion:
17.10.2007
Dokument erstellt am:
30.11.2007
Promotionsantrag am:
13.06.2007
Dateien geändert am:
03.12.2007
Medientyp:
Text