Steinmann Camia, Landsverk Megan L, Barral José M, Boehning Darren
Department of Neuroscience and Cell Biology, University of Texas Medical Branch, Galveston, Texas 77555-0620, USA.
J Biol Chem. 2008 May 16;283(20):13506-9. doi: 10.1074/jbc.C800029200. Epub 2008 Mar 25.
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.
肿瘤细胞通过策略性地下调Fas受体表达来逃避免疫攻击，并上调Fas配体的表达以促进浸润性T淋巴细胞的凋亡。许多导致细胞凋亡性死亡的途径都需要从肌醇1,4,5-三磷酸受体（IP3Rs）释放钙。在这里，我们表明SW620结肠癌细胞对Jurkat T淋巴瘤细胞的Fas依赖性杀伤需要从IP3R释放钙。IP3R信号的普遍抑制显著降低了SW620介导的Jurkat细胞凋亡。值得注意的是，一种从IP3R释放凋亡钙的特异性抑制剂强烈阻断了淋巴细胞凋亡。因此，从IP3R释放凋亡钙的选择性药理学靶向可能增强肿瘤细胞的免疫原性。
