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An anti-apoptotic role for NGF receptors in human rhabdomyosarcoma

A Astolfi1, P Nanni, L Landuzzi

  • 1Department of Experimental Pathology, Section of Cancer Research, University of Bologna, viale Filopanti 22, I-40126, Bologna, Italy.

European Journal of Cancer (Oxford, England : 1990)
|August 31, 2001
PubMed

Insights

Rhabdomyosarcoma cells express Nerve Growth Factor (NGF) receptors, which protect them from apoptosis. This suggests NGF signaling contributes to cancer cell survival by inhibiting programmed cell death.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • Rhabdomyosarcoma is a pediatric soft tissue sarcoma.
  • Nerve Growth Factor (NGF) and its receptors play roles in neuronal development and survival.
  • The role of NGF signaling in rhabdomyosarcoma remains incompletely understood.

Purpose of the Study:

  • To investigate the expression and function of NGF receptors in rhabdomyosarcoma cell lines.
  • To determine the effect of NGF on rhabdomyosarcoma cell apoptosis.
  • To explore the potential autocrine role of NGF in rhabdomyosarcoma survival.

Main Methods:

  • Analysis of NGF receptor (TrkA and p75(NTR)) expression in rhabdomyosarcoma cell lines.
  • Treatment of cell lines with exogenous NGF and assessment of cell growth, differentiation, and apoptosis.
  • Detection of endogenous NGF and neurotrophins in cell culture supernatants.
  • Inhibition of the putative autocrine NGF loop using an anti-NGF antibody.

Main Results:

  • All studied rhabdomyosarcoma cell lines expressed both TrkA and p75(NTR) NGF receptors.
  • Exogenous NGF significantly inhibited spontaneous and induced apoptosis (serum starvation, cycloheximide) without altering cell growth or differentiation.
  • Rhabdomyosarcoma cells produced endogenous NGF, and blocking this autocrine loop increased apoptosis.

Conclusions:

  • The presence of both high and low affinity NGF receptors in rhabdomyosarcoma cells is confirmed.
  • NGF signaling, potentially through an autocrine loop, contributes to the resistance to apoptosis in rhabdomyosarcoma.
  • Targeting NGF signaling may represent a therapeutic strategy for rhabdomyosarcoma.

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