Untersuchungen zur Angiogenese des Burkitt-Lymphoms unter besonderer Berücksichtigung des Lymphocyte enhancer-binding factor-1

Untersuchungen zur Angiogenese des Burkitt-Lymphoms unter besonderer Berücksichtigung des Lymphocyte enhancer-binding factor-1

Examination of Burkitt lymphoma´s angiogenesis with special consideration of Lymphocyte enhancer binding factor-1

Pia Josefa Wilming

Doctoral thesis

Date of Examination: 2017-11-29

Date of issue: 2017-11-03

Advisor: Kube, Dieter Prof. Dr.

Referee: Kube, Dieter Prof. Dr.

Referee: Wilting, Jörg Prof. Dr.

Persistent Address: http://hdl.handle.net/11858/00-1735-0000-0023-3F55-9

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Abstract

English

Burkitt´s Lymphoma (BL), derived from abnormal germinal center B cells, is a highly malignant, aggressive Non-Hodgkins´s lymphoma. Aim of our study was to dissect the functional role of the transcription factor Lymphocyte enhancer binding factor-1 (LEF1), being a signature gene for BL, regarding tumor-angiogenesis. Based on preliminary studies, we used the Burkitt Lymphoma cell line BL-2 with stable LEF-1-Knockdown (KD) and examined the KD-effect in vitro and in vivo, using the CAM (chorio-allantoic membrane)-Assay as a xenograft tumor model. We have shown that in contrast to LEF1 deficient tumors, LEF1 expressing tumors are well supplied with blood and show hemorrhagic necrosis, indicating that LEF1 influences vascularization. Furthermore the LEF1 KD tumors tend to use pre-existing blood vessels (vessel co-option). In addition we analyzed cell migration in vitro, using the Boyden chamber assay to confirm our results. Assuming that LEF1 affects angiogenesis in BL, this could be regarded in therapeutic inhibition of LEF1 in BL to improve BL´s healing opportunities.

Keywords: LEF1; Burkitt Lymphoma; CAM-Assay; tumor angiogenesis; vessel co-option