Role of VEGFA, CXCR4 and VHL mutation in tumour behaviour

Roeliene Kruizinga

    Research output: ThesisThesis fully internal (DIV)

    1560 Downloads (Pure)


    Von Hippel Lindau (VHL) disease is rare cancer syndrome. VHL disease patients develop both benign and malignant vascularised tumours. A loss-of-function of the VHL protein in VHL-disease causes increased transcription of vascular endothelial growth factor (VEGF-A), and chemokine receptor 4 (CXCR4). The aim of this thesis was to elucidate clinical features and shed more light on the behaviour of VHL-disease. In addition, the role of CXCR4 in VHL-disease and VEGFA in AML, acute myeloid leukaemia, was studied. The most important results of our research were the ability to calculate when patients will develop their first tumour by using statistical models and that intensified surveillance in pregnancy was needed. We performed a literature search that indicated the important role of CXCR4 in the interaction with the cancer micro-environment in addition to the role in metastasis. By interaction with the microenvironment cancer cells might become insensitive to standard chemotherapy. In paediatric AML we found that the measured levels of the mRNA VEGFA isoforms had no prognostic value. In addition, we found that CXCR4 and VEGFA have a higher expression in haemangioblastoma tissue compared to normal brain tissue. Moreover, CXCR4 was not expressed in normal brain tissue. These results encourage future research on treatment opportunities with drugs specifically targeting CXCR4 and VEGFA in VHL-related tumours.
    Translated title of the contributionRol van VEGFA, CXCR4 en VHL mutatie in tumor karakter
    Original languageEnglish
    QualificationDoctor of Philosophy
    Awarding Institution
    • University of Groningen
    • Links, Thera, Supervisor
    • de Vries, Liesbeth, Supervisor
    • Walenkamp, Annemiek, Co-supervisor
    • Lips, C. J. M., Assessment committee, External person
    • Verheul, Henk M. W., Assessment committee, External person
    • Vellenga, Edo, Supervisor
    Award date28-Apr-2014
    Place of Publication[S.l.]
    Print ISBNs978-90-367-6876-4
    Electronic ISBNs978-90-367-6875-7
    Publication statusPublished - 2014

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