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Fibroblast growth factors (FGFs) are important regulators of cell proliferation and differentiation. In neoplastic growth, they act as powerful mitogens inducing cell migration and invasion. Since some cancer-relevant FGFs are tightly bound to the extracellular matrix (ECM), their release is one of the critical steps in FGF bioactivation. The FGF-binding protein (FGF-BP) is a secreted, heparin-binding protein that interacts with certain FGFs, releasing them from their extracellular storage. Hence, FGF-BP plays a significant role in FGF bioactivation. It has been shown to interact non-covalently with FGF1, FGF2, FGF7, FGF10 and FGF22. FGF-BP is upregulated in several tumors and it is associated in particular with early stages of tumor formation, where angiogenesis plays a critical role. In a nude-mouse model FGF-BP is a rate-limiting factor in tumor growth. In this thesis, various knockdown strategies were explored to examine the contribution of FGF-BP to proliferation and apoptosis. By means of vector-based RNAi, isogenic colon carcinoma cell lines with permanently reduced FGF-BP levels were generated. It was shown that depletion of endogenous FGF-BP exerts anti-proliferative as well as pro-apoptotic effects in tumor cells. By selection of several clones with a robust gene knockdown, a dose-dependence of cell proliferation and apoptosis on the FGF-BP expression was established. To address the underlying cellular and molecular mechanisms in more detail, a variety of methods including flow cytometry, protease assays and Western blotting were emplyed. Compared to the parental cells the knockdown-phenotype exhibited distinct changes in cellular survival-, MAPK- and apoptosis signalling. FGF-BP downregulation induced increased levels of BH3-only domain proteins Bad and Bax, leading to enhanced Caspase 3/7 activity. In parallel, suppression of Akt kinases, activation of SAPK/ JNK and increased levels of GSK3β were detected. Alterations in the cell cycle distribution upon knockdown of FGF-BP with a marked increase of cells in the G0/G1-Phase could be demonstrated by FACS analysis. Additionally, upregulation of p21WAF1/CIP1 protein and cell cycle prolongation were observed. Furthermore, these loss-of-function mutants showed alterations in O2 consumption and in the redox status. Antibody arrays revealed increased levels of HIF1α and downregulation of catalase, indicating an impaired protection of cancer cells against oxidative stress upon depletion of FGF-BP. In a cervical cancer model it could be demonstrated that ribozyme-mediated reduction of FGF-BP led to altered sensitivities towards certain anticancer drugs. Synergistic effects of FGF-BP knockdown and chemotherapy were observed in the case of the topoisomerase I inhibitor irinotecan but not for microtubule-interfering agents emphasizing the cell cyle phase dependency of FGF-BP action. Beyond these in vitro experiments, an RNAi-based treatment study for therapeutic inhibition of FGF-BP in vivo was performed. Through polyethylenimine-based polymeric nanoparticles, siRNA-delivery was achieved that resulted in a specific FGF-BP knockdown and tumor-inhibiting effects in an s.c. colon carcinoma model. In order to screen for novel binding partners of FGF-BP, full-length FGF-BP as well as various mutant FGF-BP deletion constructs were cloned and recombinantly expressed. Protein-protein interaction studies revealed new ligands for FGF-BP within the FGF family (FGF4, FGF8). Moreover, the DNA-associated high-mobility group A (HMGA) protein was identified as a new binding partner for FGF-BP. In vitro stabilization assays revealed the affinity of FGF-BP to nucleic acids. In the presence of genomic DNA enhanced protein stability was observed. Taken together, these data support the hypothesis of a recently discovered and so far unexplored intracellular mechanism of FGF-BP action. In conclusion, this thesis elucidates the role of FGF-BP in a complex network of cytoprotective and proliferative effects. It could be demonstrated that the selective depletion of FGF-BP increases the cellular rate of apoptosis and causes cell cycle prolongation, leading to reduced tumor growth. Moreover, the findings allow to better evaluate the efficacy of an antitumoral therapy based on the knockdown of FGF-BP expression. Thus, FGF-BP represents a promising therapeutic target in the treatment of cancer.