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Analysis of Retinoic Acid-induced Neural Differentiation of Mouse Embryonic Stem Cells in Two and Three-dimensional Embryoid Bodies
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Analysis of Retinoic Acid-induced Neural Differentiation of Mouse Embryonic Stem Cells in Two and Three-dimensional Embryoid Bodies

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Nerve growth factor and retinoic acid interactions in the control of small cell lung cancer proliferation

Chiara Fiorentini1, Marco Facchetti, Alessandra Finardi

  • 1Division of Pharmacology, Department of Biomedical Sciences and Biotechnology, University of Brescia, Via Valsabbina 19, 25124 Brescia, Italy.

European Journal of Endocrinology
|September 6, 2002
PubMed
Abstract

Insights

Retinoic acid (RA) enhances nerve growth factor (NGF) receptor expression in small cell lung cancer (SCLC) cells. Combined RA and NGF treatments permanently inhibit SCLC proliferation, suggesting a novel therapeutic strategy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • Nerve growth factor (NGF) exhibits antiproliferative and differentiating effects in neuroendocrine tumors, including small cell lung cancer (SCLC).
  • NGF treatment in SCLC cell lines enhances NGF receptor expression, stimulates NGF secretion, inhibits proliferation, and reduces invasion.
  • The antiproliferative effects of NGF are transient and lost upon NGF withdrawal, necessitating the identification of co-operative factors for sustained SCLC control.

Purpose of the Study:

  • To investigate the potential interaction between NGF and retinoic acid (RA) in controlling SCLC cell proliferation.
  • To determine if RA can potentiate or sustain the antiproliferative effects of NGF in SCLC.

Main Methods:

  • SCLC cell lines (NCI-N-592 and GLC8) were treated with NGF (50 ng/ml) or all-trans RA (1 microM) for varying durations.
  • Cell proliferation was quantified using the [3H]thymidine incorporation assay.
  • NGF receptor (trkA and p75) expression was assessed via immunofluorescence.

Main Results:

  • RA treatment significantly increased the expression of trkA and p75 NGF receptors in SCLC cell lines.
  • RA prevented the downregulation of NGF production and NGF receptor expression observed after NGF withdrawal.
  • RA abolished the increase in cell proliferation associated with NGF withdrawal, both in vitro and in vivo, thereby rendering NGF's antiproliferative effects permanent.

Conclusions:

  • Combined treatment with NGF and RA, or drugs mimicking their effects, presents a promising therapeutic strategy for SCLC.
  • This synergistic approach may offer a method to achieve sustained inhibition of SCLC growth and differentiation.

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