Angiogenesis in tumor and adjacent non - tumorous parenchyma - molecular presentation before and after therapy

Gesiena van der Wal

    Research output: ThesisThesis fully internal (DIV)

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    For tumor growth, angiogenesis or new blood vessel formation from pre-existing blood vessels, is essential. Other than the tumor itself, the tumor microenvironment is an important source of angiogenic molecules as well. The angiogenic status of glioblastomas, colorectal liver metastases (CRLM), gastroenteropancreatic neuroendocrine liver metastases (GEP-NETM), and hepatocellular carcinomas (HCC) and their adjacent non-tumorous environment have not yet been investigated to their full extent. In this thesis we aimed to gain insight in the angiogenic status of these tumors and their environment - with or without treatment- both on a molecular level and immunohistochemically.
    We demonstrated that a combination therapy consisting of COX-2 inhibitor and radiotherapy is a promising treatment for glioblastoma tumor volume reduction, affecting the tumor vasculature in mice. In primary and secondary human liver tumors, we revealed that adjacent liver parenchyma (of CRLM perse as well as after treatment with anti-angiogenic combination therapy and HCC) showed high expression levels of angiogenic molecules. Possibly, adjacent liver parenchyma functions as a favorable angiogenic soil that can stimulate tumor growth. With regard to HCC and GEP-NETM we found a different gene expression of angiogenic molecules, despite a similar radiological hypervascular appearance. Additionally, radiological hypervascular GEP-NETM showed a lower expression level of angiogenic molecules compared to hypovascular CRLM. These novel insights in angiogenic profiles of the different tumor types and especially of the adjacent liver parenchyma may have important implications for therapeutic choices regarding anti-angiogenic treatments of the primary tumors and metastases investigated.
    Translated title of the contributionAngiogenese in tumor en aangrenzend niet-tumorhoudend weefsel - moleculaire presentatie voor en na therapy
    Original languageEnglish
    QualificationDoctor of Philosophy
    Awarding Institution
    • University of Groningen
    • Molema, Ingrid, Supervisor
    • Gouw, Annette, Supervisor
    • de Jong, Koert, Co-supervisor
    Award date26-Nov-2014
    Place of Publication[S.l.]
    Print ISBNs978-90-367-7450-5
    Electronic ISBNs978-90-367-7449-9
    Publication statusPublished - 2014

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