Targeting FPR1 and CXCR4 in cancer and the contribution of the tumor microenvironment

Jennifer Boer

    Research output: ThesisThesis fully internal (DIV)

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    Abstract

    Solid tumors can be primarily resistant or could become resistant to therapy, due to the protective effect of their direct tumor environment, which is called the microenvironment. UMCG-researcher Jennifer Boer studied the interaction of glioblastoma (GBM) and prostate cancer cells with their tumor microenvironment. In this context she investigated the role of two membrane bound proteins (receptors) called formyl peptide receptor-1 (FPR1) and chemokine receptor-4 (CXCR4).
    From laboratory research it became evident that both receptors are involved in the migration and possible dissemination of tumor cells, which migrate towards their ligands present in the microenvironment. The ligands for FPR1 are formyl-methionil-leucine-lysine-isoleucine-valine (fMLKLIV) and formyl-methionil-methionil-tyrosine-alanine-leucine-phenylalanine (fMMYALF), which are released when unregulated cell death occurs. Jennifer Boer used the chemotaxis inhibitory protein of S. aureus (CHIPS), in order to inhibit the migration of FPR1-positive tumor cells. In a preclinical setting the use of this bacterial derived protein led to a slight survival improvement. When CXCR4 is activated by its ligand CXCL12, the receptor contributes to tumor cell mobility but also to therapy resistance mediated by the tumor microenvironment. The CXCR4 inhibitor AMD3100 transiently sensitizes prostate cancer cells to radiation therapy but eventually leads to an increase of circulating tumor cells. According to Jennifer Boer this is an important aspect that should be taken in consideration when designing future clinical trials that involve the use of CXCR4 inhibitors. She concludes that therapies targeting FPR1 and CXCR4 may contribute to the development of new cancer treatments.
    Original languageEnglish
    QualificationDoctor of Philosophy
    Awarding Institution
    • University of Groningen
    Supervisors/Advisors
    • de Vries, Liesbeth, Supervisor
    • van Strijp, Jos, Supervisor, External person
    • Walenkamp, Annemiek, Co-supervisor
    • den Dunnen, Wilfred, Co-supervisor
    • Timmer-Bosscha, Hetty, Co-supervisor
    • Boddeke, Erik, Assessment committee
    • van der Valk, Paul, Assessment committee, External person
    • Koenderman, Leo, Assessment committee, External person
    Award date15-Jun-2015
    Place of Publication[Groningen]
    Publisher
    Print ISBNs978-90-367-7914-2
    Electronic ISBNs978-90-367-7919-7
    Publication statusPublished - 2015

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