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

Min-Suk Kim1, Chong Jai Kim, Hyun Sook Jung

  • 1Department of Pathology, Seoul National University College of Medicine, Seoul, Korea.

The Journal of Pathology
|December 25, 2003
PubMed

Insights

Fibroblast growth factor 2 (FGF2) induces neuronal differentiation and apoptosis in peripheral primitive neuroectodermal tumour (PNET) cells, including Askin tumour. This highlights FGF2 signaling as a potential therapeutic target for PNET.

Area of Science:

  • Molecular Biology
  • Oncology
  • Cell Signaling

Background:

  • Peripheral primitive neuroectodermal tumour (PNET)/Ewing's sarcoma (ES) and neuroblastoma (NB) are neural crest-derived tumors.
  • Fibroblast growth factor 2 (FGF2) influences neural crest cell biology, inducing apoptosis in PNET/ES and variable effects in NB.
  • The JK-GMS Askin tumor cell line differentiates with nerve growth factor (NGF), confirming differentiation machinery integrity.

Purpose of the Study:

  • To investigate whether FGF2 can induce differentiation in JK-GMS PNET cells.
  • To elucidate the signaling pathways involved in FGF2-mediated effects in PNET cells.
  • To compare FGF2 effects across different PNET and ES cell lines.

Main Methods:

  • Treatment of JK-GMS cells with FGF2 and pathway inhibitors (PD98059 for MEK1, JNK inhibitor).
  • Assessment of FGFR phosphorylation, ERK1/2 and JNK activation.
  • Analysis of biological effects including growth, differentiation, apoptosis, and gene expression (neurofilaments, c-myc, bcl-2, caspase 3).

Main Results:

  • FGF2 treatment activated FGFR1, ERK1/2, and JNK pathways in JK-GMS cells.
  • FGF2 induced growth inhibition, neuronal differentiation, apoptosis, increased neurofilaments, and altered c-myc/bcl-2 expression.
  • FGF2 promoted significant neuronal differentiation in the SK-N-MC PNET cell line, but not in CADO-ES or RD-ES Ewing's sarcoma cell lines.

Conclusions:

  • FGF2 effectively induces neuronal differentiation and apoptosis in PNET, including Askin tumor cells.
  • The ERK1/2 and JNK signaling pathways are critical mediators of FGF2's effects in PNET cells.
  • The FGF2 signaling pathway represents a promising therapeutic target for PNET.

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