Requirement of inositol 1,4,5-trisphosphate receptors for tumor-mediated lymphocyte apoptosis.
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.
Steinmann
Camia
C
Department of Neuroscience and Cell Biology, University of Texas Medical Branch, Galveston, Texas 77555-0620, USA.
Landsverk
Megan L
ML
Barral
José M
JM
Boehning
Darren
D
D017209:Apoptosis; D002118:Calcium / Q000737:chemistry; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D006801:Humans; D007107:Immune System; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000378:metabolism / Q000502:physiology*; D019169:Jurkat Cells; D008214:Lymphocytes / Q000378:metabolism / Q000473:pathology*; D008954:Models, Biological; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology*; D010455:Peptides / Q000737:chemistry; D034622:RNA Interference; D013601:T-Lymphocytes / Q000378:metabolism; D019014:fas Receptor / Q000737:chemistry
D053496:Inositol 1,4,5-Trisphosphate Receptors; D010455:Peptides; D019014:fas Receptor; D053148:Caspase 3; D002118:Calcium