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Mechanisms of resistance of normal cells to TRAIL induced apoptosis vary between different cell types

X D Zhang1, T Nguyen, W D Thomas

  • 1The Oncology and Immunology Unit, Newcastle Mater Hospital, David Maddison Building, Room 443, Cnr. King and Watt Streets, 2300, Newcastle, N.S.W., Australia.

FEBS Letters
|October 12, 2000
PubMed

Insights

Normal cells resist tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) apoptosis through various mechanisms. Decoy receptor expression and localization determine TRAIL resistance in different cell types, impacting endothelial cells, melanocytes, and fibroblasts.

Area of Science:

  • Cell Biology
  • Apoptosis Research
  • Molecular Mechanisms of Cell Death

Background:

  • Normal cells resist tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis.
  • This resistance is often attributed to decoy receptors.
  • The precise mechanisms and cellular variations in TRAIL resistance are not fully elucidated.

Purpose of the Study:

  • To investigate the varying expression and localization of TRAIL receptors (TRAIL-Rs) in different normal cell types.
  • To identify the distinct mechanisms conferring resistance to TRAIL-induced apoptosis.
  • To determine the role of decoy receptors and intracellular factors in cellular resistance.

Main Methods:

  • Analysis of TRAIL receptor expression and subcellular localization across different normal cell types.
  • Investigation of apoptosis pathways downstream of caspase-3.
  • Comparative studies on endothelial cells, melanocytes, and fibroblasts.

Main Results:

  • TRAIL receptor expression and localization differ significantly between cell types.
  • The decoy receptor TRAIL-R3 is crucial for protecting endothelial cells.
  • Melanocytes and fibroblasts utilize distinct mechanisms, including lack of surface death receptor expression and intracellular inhibitors, for TRAIL resistance.

Conclusions:

  • Cellular resistance to TRAIL-induced apoptosis is mediated by diverse mechanisms.
  • Differential subcellular localization of decoy receptors is a key factor in their effectiveness.
  • Understanding these varied resistance strategies is vital for TRAIL-based therapeutic development.

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