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Death receptor pathways mediate targeted and non-targeted effects of ionizing radiations in breast cancer cells

Audrey Luce1, Aurélie Courtin, Céline Levalois

  • 1CEA, DSV, iRCM, SREIT, Laboratoire de Cancérologie Expérimentale, Fontenay-aux-Roses, France.

Carcinogenesis
|January 8, 2009
PubMed

Insights

Delayed cell death in solid tumors after gamma-irradiation involves Fas, TRAIL, and TNF-alpha death receptor pathways. These pathways mediate apoptosis and affect bystander cells, offering new therapeutic targets for cancer treatment.

Area of Science:

  • Oncology
  • Cell Biology
  • Radiation Biology

Background:

  • Delayed cell death via mitotic catastrophe is common in solid tumors post-gamma-irradiation.
  • Mechanisms driving early radiation-induced cell death are known, but delayed death mechanisms remain unclear.

Purpose of the Study:

  • To elucidate the molecular mechanisms of delayed cell death in breast cancer cells following gamma-irradiation.
  • To investigate the role of death receptor pathways in radiation-induced apoptosis.

Main Methods:

  • Analysis of Fas, TRAIL, and TNF-alpha death receptor and ligand expression after irradiation.
  • Experimental treatments using TNF-alpha, TRAIL, and anti-Fas antibodies.
  • Assessment of apoptosis induction and neutralization of death receptor pathways.
  • Detection of soluble ligand excretion by irradiated cells.

Main Results:

  • Gamma-irradiation increases expression of Fas, TRAIL-R, and TNF-R, sensitizing cells to apoptosis.
  • Later, increased FasL, TRAIL, and TNF-alpha expression promotes apoptosis linked to mitotic catastrophe.
  • Irradiated cells release soluble ligands that induce bystander cell death.
  • Blocking death receptor pathways inhibits delayed radiation-induced cell death.

Conclusions:

  • Fas, TRAIL, and TNF-alpha death receptor pathways are critical mediators of delayed apoptosis after gamma-irradiation.
  • These pathways are involved in both targeted and non-targeted effects of ionizing radiation on cancer cells.
  • The findings identify key molecular players in radiation-induced delayed cell death, suggesting potential therapeutic strategies.

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