Targets in the microenvironment of rectal cancer: A focus on angiogenic growth factors and chemokines

Karin Rita Tamas

    Research output: ThesisThesis fully internal (DIV)

    1693 Downloads (Pure)

    Abstract

    Cancer cells interact with each other, and with cells of the tumor microenvironment. This coincides with the production of numerous soluble factors which can stimulate cancer cell growth and migration. In addition the tumor microenvironment can facilitate cancer cells to escape the effect of anticancer treatment. Understanding how the cross-talk between cancer and non-cancer cells in the tumor microenvironment mediates disease progression and resistance to treatment can potentially help to define novel and more successful treatments. In this thesis we therefore studied vessel growth factors and migration factors in metastatic rectal cancer. These patients received radiotherapy for their rectal cancer and systemic therapy including an antibody bevacizumab, that binds to the vessel growth stimulation factor VEGF-A. This treatment allowed subsequent surgical removal of the tumor in the rectum and the metastases in the liver and lungs in 72% of the patients. By examining the protein expression profile of growth and migration factors in rectal cancer cells and neighboring connecting non-cancer cells before and after the aforementioned therapy, we identified placental growth factor (PlGF) and the chemokine ligand CXCL12/ chemokine receptor CXCR4 pair as potential drug targets for rectal cancer therapy.
    Original languageEnglish
    QualificationDoctor of Philosophy
    Awarding Institution
    • University of Groningen
    Supervisors/Advisors
    • Hospers, Geke, Supervisor
    • de Vries, Liesbeth, Supervisor
    • Walenkamp, Annemiek, Co-supervisor
    • Wiggers, Theo, Assessment committee
    • Hollema, Harry, Assessment committee
    • Richel, Dick J., Assessment committee, External person
    Award date19-Oct-2015
    Place of Publication[Groningen]
    Publisher
    Print ISBNs978-90-367-8108-4
    Electronic ISBNs978-90-367-8107-7
    Publication statusPublished - 2015

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