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Die Rolle des Transkriptionsfaktors LEF-1 im Hodgkin-Lymphom

dc.contributor.advisorKube, Dieter Prof. Dr.
dc.contributor.authorHarenberg, Moritz
dc.titleDie Rolle des Transkriptionsfaktors LEF-1 im Hodgkin-Lymphomde
dc.title.translatedThe role of the transcription factor LEF-1 in classical Hodgkin lymphomade
dc.contributor.refereeKube, Dieter Prof. Dr.
dc.description.abstractengClassical Hodgkin lymphoma (cHL) is one of the most common malignant lymphomas. The malignant cells in cHL form only a small part of the tumour, whereas the majority consists of a reactive infiltrate of stromal cells and cells of the immune system. Therefore, the interaction between the malignant cells and their microenvironment is of great importance. Deregulated intracellular signalling pathways are one example of this interaction. The canonic Wnt signalling pathway and its transcription factor LEF-1 are deregulated in various malignant diseases, such as colon or breast cancer. So far, there is only limited data about the importance of canonic Wnt signalling in Hodgkin lymphoma. To examine this, a stable LEF-1 knockdown in the HL cell line L-428 has been established by two separate lentiviral transductions. Using the xenograft model of the chick chorio-allantoic membrane assay (CAM assay), cHL tumour formation and the effect of LEF-1 knockdown on it have been studied. Furthermore, the involvement of LEF-1 in the interaction between HL cells and endothelial cells of the microenvironment has been examined. In the CAM assay, it could be shown that HL cells form tumours with signs of massive bleeding. Using histological methods, the tumour vessels showed bizarre and irregular configurations with surrounding haemorrhages. Additionally, a complete lack of lymphatic vessels in HL tumours has been observed. Knockdown of LEF-1 led to the formation of significantly smaller tumours in one of the two transduced cell lines. LEF-1 had no effect on the size or intensity of the tumour haemorrhages. In migration assays using HUVEC cell lines conditioned media of HL cells stimulated migration of endothelial cells. This stimulation of endothelial cell migration by the HL cells is partly dependent on LEF-1 and could be mediated by a LEF-1 regulated secretion of VEGF-A, a major angiogenic growth factor. These data describe for the first time the effect of the transcription factor LEF-1 in Hodgkin lymphoma and characterize it as a possible tumour progression factor. LEF-1 seems to have an influence on tumour growth and can contribute to the stimulation of endothelial cell migration by HL cells. Thus, LEF-1 could potentially be a future therapeutic target in classical Hodgkin
dc.contributor.coRefereeBastians, Holger Prof. Dr.
dc.subject.enghodgkin lymphomade
dc.affiliation.instituteMedizinische Fakultätde
dc.subject.gokfullInnere Medizin - Allgemein- und Gesamtdarstellungen (PPN619875747)de
dc.subject.gokfullBiologie (PPN619875151)de

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