Fibroblast growth factor 2 induces differentiation and apoptosis of Askin tumour cells.

Peripheral primitive neuroectodermal tumour (PNET)/Ewing's sarcoma (ES) and neuroblastoma (NB) are related tumours of neural crest origin with primitive neural characteristics. Fibroblast growth factor 2 (FGF2) is a critical signalling molecule for primitive neural crest cells. The treatment of NB cells with FGF2 variably affects biological characteristics such as growth and differentiation, while in PNET/ES, FGF2 predominantly induces apoptosis. The JK-GMS Askin tumour cell line can be induced to differentiate upon treatment with nerve growth factor (NGF), indicating the integrity of the cellular machinery necessary for differentiation. The present study assesses whether FGF2 can induce differentiation in JK-GMS cells. JK-GMS cells expressed high-affinity FGF receptors (FGFRs), and treatment with FGF2 induced phosphorylation of FGFR1 together with activation of extracellular signal-regulated kinases (ERK1/ERK2) and c-Jun N-terminal kinase (JNK). Subsequent biological effects were growth inhibition, neuronal differentiation, and apoptosis, and these changes were associated with increased expression of neurofilaments, reduction of c-myc and bcl-2 expression, and activation of caspase 3. Treatment of the cells with a specific inhibitor of the MAPK/extracellular signal-regulated kinase (MEK)-1, PD98059, predominantly inhibited the effects of FGF2 on growth, differentiation, and apoptosis, while an inhibitor of JNK reduced apoptosis, indicating that the ERK1/2 and JNK pathways are critical components of FGF2-mediated effects in JK-GMS cells. Additional comparative analyses of FGF2-mediated effects in two ES cell lines (CADO-ES, RD-ES) and a PNET cell line (SK-N-MC) showed pronounced differentiation in SK-N-MC, but not in CADO-ES or RD-ES cells. This study demonstrates that FGF2 can induce neuronal differentiation of PNET including Askin tumour. These findings clearly indicate that the FGF2-mediated signalling pathway plays a critical role in controlling the major properties of PNET cells and may provide a potential therapeutic target for PNET.

Kim MS ，Kim CJ ，Jung HS ，Seo MR ，Juhnn YS ，Shin HY ，Ahn HS ，Thiele CJ ，Chi JG ... -  《JOURNAL OF PATHOLOGY》

Both FGF1 and bcl-x synthesis are necessary for the reduction of apoptosis in retinal pigmented epithelial cells by FGF2: role of the extracellular signal-regulated kinase 2.

Bryckaert M ，Guillonneau X ，Hecquet C ，Courtois Y ，Mascarelli F ... -  《ONCOGENE》

Disruption of fibroblast growth factor signal pathway inhibits the growth of synovial sarcomas: potential application of signal inhibitors to molecular target therapy.

Ishibe T ，Nakayama T ，Okamoto T ，Aoyama T ，Nishijo K ，Shibata KR ，Shima Y ，Nagayama S ，Katagiri T ，Nakamura Y ，Nakamura T ，Toguchida J ... -  《CLINICAL CANCER RESEARCH》

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

Sturla LM ，Westwood G ，Selby PJ ，Lewis IJ ，Burchill SA ... -  《CANCER RESEARCH》

Heparan sulfate proteoglycans function as receptors for fibroblast growth factor-2 activation of extracellular signal-regulated kinases 1 and 2.

Chua CC ，Rahimi N ，Forsten-Williams K ，Nugent MA ... -  《-》