1. Requirement of Inositol 1,4,5-Trisphosphate Receptors for Tumor-mediated Lymphocyte Apoptosis.
- Author
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Steinmann, Camia, Landsverk, Megan L., Barral, José M., and Boehning, Darren
- Subjects
- *
INOSITOL , *LYMPHOCYTES , *APOPTOSIS , *CELL death , *TUMORS , *LIGANDS (Biochemistry) - 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. [ABSTRACT FROM AUTHOR]
- Published
- 2008
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