Loss of Sparc in p53-null Astrocytes Promotes Macrophage Activation and Phagocytosis Resulting in Decreased Tumor Size and Tumor Cell Survival.
Loss of Sparc in p53-null Astrocytes Promotes Macrophage Activation and Phagocytosis Resulting in Decreased Tumor Size and Tumor Cell Survival.
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p53 缺失星形胶质细胞中 Sparc 的缺失促进巨噬细胞激活和吞噬作用，导致肿瘤大小和肿瘤细胞存活率下降。
DOI：
10.1111/bpa.12161
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发表时间：
2015
期刊：
影响因子：
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通讯作者：
Rempel,SandraA
中科院分区：
文献类型：
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作者：
Thomas,StaceyL;Schultz,ChadR;Mouzon,Ezekiell;Golembieski,WilliamA;ElNaili,Reima;Radakrishnan,Archanna;Lemke,Nancy;Poisson,LailaM;Gutiérrez,JorgeA;Cottingham,Sandra;Rempel,SandraA
胶质瘤早期发生的变化包括诱导p53表达和p53肿瘤抑制基因的缺失。p53和p53通过对凋亡信号的反向作用调节胶质瘤细胞的存活。因此，在胶质瘤形成过程中，p53的缺失可能与p53的上调协同作用，从而提高细胞存活率。这项研究确定了Sparcin缺失p53是否会导致体内异种移植脑肿瘤模型中细胞存活率降低、肿瘤形成以及肿瘤免疫原性增加。在体外，Sparcinp 53缺失星形胶质细胞的缺失导致细胞增殖增加，但致瘤性丧失。在颅内植入后7天，Sparc-null肿瘤的肿瘤细胞存活率、增殖率降低，肿瘤尺寸缩小。Sparc的缺失促进了小胶质细胞/巨噬细胞的活化和对肿瘤细胞的吞噬作用。我们的研究结果表明，在胶质瘤形成的早期阶段，p53的缺失/突变可能与诱导的p53协同作用，以增强癌细胞的存活和逃避免疫监视。
Both the induction of SPARC expression and the loss of the p53 tumor suppressor gene are changes that occur early in glioma development. Both SPARC and p53 regulate glioma cell survival by inverse effects on apoptotic signaling. Therefore, during glioma formation, the upregulation of SPARC may cooperate with the loss of p53 to enhance cell survival. This study determined whether the loss ofSparcin astrocytes that are null forp53would result in reduced cell survival and tumor formation and increased tumor immunogenicity in anin vivoxenograft brain tumor model.In vitro, the loss ofSparcinp53‐null astrocytes resulted in an increase in cell proliferation, but a loss of tumorigenicity. At 7 days after intracranial implantation,Sparc‐null tumors had decreased tumor cell survival, proliferation and reduced tumor size. The loss ofSparcpromoted microglia/macrophage activation and phagocytosis of tumor cells. Our results indicate that the loss ofp53by deletion/mutation in the early stages of glioma formation may cooperate with the induction of SPARC to potentiate cancer cell survival and escape from immune surveillance.