Stress-induced release of HSC70 from human tumors
Stress-induced release of HSC70 from human tumors
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DOI：
10.1016/s0008-8749(03)00115-1
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发表时间：
2003-04-01
影响因子：
4.3
通讯作者：
Fiorentino, S
中科院分区：
文献类型：
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作者：
Barreto, A;Gonzalez, JM;Fiorentino, S
在这项研究中，我们证明，促炎细胞因子干扰素-γ（IFN-γ）诱导的70-kDa热休克蛋白（HSC 70）的组成形式从K562红白血病细胞的主动释放。用IFN-γ处理K562细胞以蛋白酶体依赖的方式诱导70-kDa热休克蛋白（HSP 70）的诱导型上调，但不诱导胞浆内HSC 70的组成型上调。此外，IFN-γ诱导表面结合的HSC 70的下调，但没有显着改变表面结合的HSP 70的表达。这些发现表明，HSC 70可以从肿瘤细胞中主动释放，并且表明免疫调节剂刺激细胞内HSC 70释放的先前未知的机制。这一机制可能解释了最近在针对多种癌症的基于热休克蛋白的免疫疗法期间观察到的热休克蛋白的强效伴侣因子活性。(C)2003 Elsevier Science（美国）。All rights reserved.
In this study, we demonstrate that the pro-inflammatory cytokine interferon-gamma (IFN-gamma) induces the active release of the constitutive form of the 70-kDa heat shock protein (HSC70) from K562 erythroleukemic cells. Treatment of K562 cells with IFN-gamma induced the upregulation of the inducible form of the 70-kDa heat shock protein (HSP70), but not the constitutive form of HSC70 within the cytosol, in a proteasome-dependent manner. In addition, IFN-gamma induced the downregulation of surface-bound HSC70, but did not significantly alter surface-bound HSP70 expression. These findings indicate that HSC70 can be actively released from tumor cells and is indicative of a previously unknown mechanism by which immune modulators stimulate the release of intracellular HSC70. This mechanism may account for the potent chaperokine activity of heat shock proteins recently observed during heat shock protein-based immunotherapy against a variety of cancers. (C) 2003 Elsevier Science (USA). All rights reserved.