| dc.description.abstract | Fibroblast Growth Factor Receptors (FGFRs) are crucial cell surface receptors that regulate key cellular processes upon activation. Recent studies highlight the significance of FGFR2 and FGFR4 in ovarian and breast cancer development. However, conventional 2D cell models lack the complexity of the tumor microenvironment, necessitating the use of 3D cell models (spheroids) and relevant extracellular matrices more accurate disease modeling. This study aims to establish spheroids to analyze the function of oncogenic FGFR variants in cell growth, apoptosis, and invasion. FGFR2 variants (S252W, N550K) and FGFR4 variants (V550L, G388R) transfected into HEK293 cells were studied. Cells were analyzed both pre-induction (gene induction in 2D before spheroid formation) and post-induction (gene induction after spheroid formation). Spheroids were embedded in collagen or fibrin to assess how these extracellular matrices affect the spheroid properties and cell functions.
Pre-induced spheroids were imaged at 72 hours, while post-induced spheroids were imaged daily over 96 hours under continuous induction. The results revealed variant-specific differences in growth and compactness, among other parameters. For example, post-induced spheroids of FGFR4 showed a more invasive behavior compared to FGFR2 variants. Immunofluorescence staining at 96 hours indicated distinct expression patterns and cytoskeletal organization, though staining issues affected FGFR4 and YAP expressions. Spheroids in collagen showed different growth dynamics compared to those in fibrin, suggesting matrix-specific influences on FGFR-mediated oncogenic processes. These findings demonstrate the efficacy of 3D cell models in mimicking the tumor microenvironment and provide insights into the roles of FGFR variants in cancer, offering a platform for evaluating FGFR-targeted therapies in ovarian and breast cancer. | |