Requirement of inositol 1,4,5-trisphosphate receptors for tumor-mediated lymphocyte apoptosis

J Biol Chem. 2008 May 16;283(20):13506-9. doi: 10.1074/jbc.C800029200. Epub 2008 Mar 25.

Abstract

Tumor cells strategically down-regulate Fas receptor expression to evade immune attack and up-regulate expression of Fas ligand to promote apoptosis of infiltrating T lymphocytes. Many pathways leading to apoptotic cell death require calcium release from inositol 1,4,5-trisphosphate receptors (IP3Rs). Here, we show that Fas-dependent killing of Jurkat T lymphoma cells by SW620 colon cancer cells requires calcium release from IP3R. General suppression of IP3R signaling significantly reduced SW620-mediated Jurkat cell apoptosis. Significantly, a specific inhibitor of apoptotic calcium release from IP3R strongly blocked lymphocyte apoptosis. Thus, selective pharmacological targeting of apoptotic calcium release from IP3R may enhance tumor cell immunogenicity.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis*
  • Calcium / chemistry
  • Caspase 3 / metabolism
  • Cell Line, Tumor
  • Humans
  • Immune System
  • Inositol 1,4,5-Trisphosphate Receptors / metabolism
  • Inositol 1,4,5-Trisphosphate Receptors / physiology*
  • Jurkat Cells
  • Lymphocytes / metabolism
  • Lymphocytes / pathology*
  • Models, Biological
  • Neoplasms / metabolism
  • Neoplasms / pathology*
  • Peptides / chemistry
  • RNA Interference
  • T-Lymphocytes / metabolism
  • fas Receptor / chemistry

Substances

  • Inositol 1,4,5-Trisphosphate Receptors
  • Peptides
  • fas Receptor
  • Caspase 3
  • Calcium