The potential role of basic fibroblast growth factor in malignant transformation, angiogenesis, invasion and proliferation of human gliomas.

摘要

The role of basic fibroblast growth factor (bFGF) in the malignant phenotype of human gliomas was examined in this dissertation. A bFGF ELISA, demonstrated to detect recombinant human bFGF protein, was used to quantitate bFGF protein in glioma tissue samples. Basic FGF protein was significantly elevated in low and high grade glioma tissues, suggesting increased bFGF expression could be an early event in the progression of gliomas. Because the tumor sections contained non-tumor elements, bFGF gene and protein expression were examined in established human glioma cell lines. Human glioma cells demonstrated extracellular release of bFGF and expression of higher molecular weight bFGF isoforms. Because secreted bFGF could be important in the malignant phenotype of gliomas, fibroblasts were stably transfected with an expression vector for a secreted bFGF. These cells were more invasive in vitro and in the brain. To confirm and extend these data, non-neoplastic human astrocytes were stably transfected with the bFGF secretion vector. These cells demonstrated features associated with malignant transformation, suggesting increased expression and extracellular release of bFGF could have transforming potential in human astrocytic cells. To determine if bFGF gene and protein expression were required for human glioma cell growth, bFGF-specific antisense oligodeoxynucleotides were tested. The antisense treated glioma cells demonstrated decreased bFGF gene and protein expression and significantly decreased proliferation. Taken together, the data suggests the potential importance of bFGF in glioma cell transformation and growth, and indicates anti-bFGF strategies could be useful in the management of glioma patients.