This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Sturla, L.-M. Articles by Burchill, S. A. Search for Related Content PubMed PubMed Citation Articles by Sturla, L.-M. Articles by Burchill, S. A.

Induction of Cell Death by Basic Fibroblast Growth Factor in Ewing’s Sarcoma¹

Candlelighter’s Children’s Cancer Research Laboratory [L-M. S., G. W., S. A. B.], Imperial Cancer Research Fund Cancer Medicine Research Unit [P. J. S.], and Department of Pediatric Oncology [I. J. L.], St. James’s University Hospital, Leeds LS9 7TF, United Kingdom

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, proliferation, and differentiation during embryogenesis, we have tested the hypothesis that bFGF and FGF receptors may contribute to the development of Ewing’s sarcoma and may provide a mechanism for the modulation of their behavior. All four of the Ewing’s sarcoma cell lines examined expressed bFGF and FGF receptors, which were detected by immunofluorescence and Western blotting. bFGF-induced a significant dose-dependent decrease in Ewing’s sarcoma cell proliferation on plastic and reduced anchorage-independent growth in soft agar. Unexpectedly, this decrease in cell number reflected bFGF-induced apoptosis and necrosis, as demonstrated by electron microscopy, binding of annexin V, and staining with acridine orange. Induction of cell death was dependent on dosage of, and period of exposure to, bFGF. bFGF did not induce differentiation of Ewing’s sarcoma cells in either the presence or the absence of 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 those in control mice, and showed an increased level of apoptotic nuclei. This is in contrast to the mitogenic effect bFGF has in most other cancer cells. 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 therapeutic strategy for Ewing’s sarcomas.

This article has been cited by other articles:

				C. Ma, K. A. Bower, G. Chen, X. Shi, Z.-J. Ke, and J. Luo Interaction between ERK and GSK3{beta} Mediates Basic Fibroblast Growth Factor-induced Apoptosis in SK-N-MC Neuroblastoma Cells J. Biol. Chem., April 4, 2008; 283(14): 9248 - 9256. [Abstract] [Full Text] [PDF]

				A. Bush Update in Pediatric Lung Disease 2006 Am. J. Respir. Crit. Care Med., March 15, 2007; 175(6): 532 - 540. [Full Text] [PDF]

				M. Yi, R. Belcastro, S. Shek, D. Luo, M. Post, and A. K. Tanswell Fibroblast Growth Factor-2 and Receptor-1{alpha}(IIIc) Regulate Postnatal Rat Lung Cell Apoptosis Am. J. Respir. Crit. Care Med., September 1, 2006; 174(5): 581 - 589. [Abstract] [Full Text] [PDF]

				T. Ishibe, T. Nakayama, T. Okamoto, T. Aoyama, K. Nishijo, K. R. Shibata, Y. Shima, S. Nagayama, T. Katagiri, Y. Nakamura, et al. Disruption of Fibroblast Growth Factor Signal Pathway Inhibits the Growth of Synovial Sarcomas: Potential Application of Signal Inhibitors to Molecular Target Therapy Clin. Cancer Res., April 1, 2005; 11(7): 2702 - 2712. [Abstract] [Full Text] [PDF]

				S. Dalal, A. M. Berry, C. J. Cullinane, D. C. Mangham, R. Grimer, I. J. Lewis, C. Johnston, V. Laurence, and S. A. Burchill Vascular Endothelial Growth Factor: A Therapeutic Target for Tumors of the Ewing's Sarcoma Family Clin. Cancer Res., March 15, 2005; 11(6): 2364 - 2378. [Abstract] [Full Text] [PDF]

				A. J. K. Williamson, B. C. Dibling, J. R. Boyne, P. Selby, and S. A. Burchill Basic Fibroblast Growth Factor-induced Cell Death Is Effected through Sustained Activation of p38MAPK and Up-regulation of the Death Receptor p75NTR J. Biol. Chem., November 12, 2004; 279(46): 47912 - 47928. [Abstract] [Full Text] [PDF]