Induction of cell death by basic fibroblast growth factor in Ewing's sarcoma

Ewing's sarcoma is thought to arise after developmental arrest of primitive neural cells during embryogenesis. Because basic fibroblast growth factor (bFGF) has a critical role in the regulation of cell survival, proliferatio n, and differentiation during embryogenesis, we have tested the hypothesis that bFGF and FGF receptors may contribute to the development of Ewing's sa rcoma and may provide a mechanism for the modulation of their behavior. All four of the Ewing's sarcoma cell Lines examined expressed bFGF and EGF rec eptors, which were detected by immunofluorescence and Western blotting. bFG F-induced a significant dose-dependent decrease in Erring's sarcoma cell pr oliferation on plastic and reduced anchorage-independent growth in soft aga r. Unexpectedly, this decrease in cell number reflected bFGF-induced apopto sis and necrosis, as demonstrated by electron microscopy, binding of annexi n V, and staining with acridine orange. Induction of cell death was depende nt on dosage of, and period of exposure to, bFGF. bFGF did not induce diffe rentiation of Ewing's sarcoma cells in either the presence or the absence o f serum or nerve growth factor. Treatment of NuNu mice with bFGF decreased growth of the highly tumorigenic Ewing's sarcoma cell lines. Histologically tumors grown in the NuNu mice treated with bFGF were less cellular than th ose in control mice, and showed an increased level of apoptotic nuclei. Thi s is in contrast to the mitogenic effect bFGF has in most of her cancer cel ls, In summary, bFGF decreases Ewing's sarcoma growth in vitro and in vivo by the induction of cell death. This novel observation may provide a new th erapeutic strategy for Ewing's sarcomas.