The odyssey of Hsp60 from tumor cells to other destinations includes plasma membrane-associated stages and Golgi and exosomal protein-trafficking modalities.

The odyssey of Hsp60 from tumor cells to other destinations includes plasma membrane-associated stages and Golgi and exosomal protein-trafficking modalities.
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DOI:
10.1371/journal.pone.0042008
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发表时间:
2012
期刊:
影响因子:
3.7
通讯作者:
Cappello F
Cappello F
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Campanella C;Bucchieri F;Merendino AM;Fucarino A;Burgio G;Corona DF;Barbieri G;David S;Farina F;Zummo G;de Macario EC;Macario AJ;Cappello F

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在之前的工作中,我们首次表明人类肿瘤细胞通过外泌体分泌Hsp60,外泌体被认为是参与肿瘤进展的免疫活性微泡。这一发现提出了关于Hsp60到达外泌体的途径、其在其中的位置以及Hsp60是否也可以通过其他机制分泌的问题,例如,在Golgi。我们在这里介绍的工作中解决了这些问题。我们发现,热休克蛋白60定位于肿瘤细胞质膜,与脂筏,并最终在外泌体膜。我们还发现了证据表明,热休克蛋白60定位在高尔基体和它的分泌被阻止了这个细胞器的抑制剂。我们提出了一个多阶段的过程,从内部到外部的细胞,包括蛋白质交通途径的组合,并最终在循环血液中的伴侣蛋白的易位的Hsp60。提出的新信息应有助于设计未来的研究战略和发展诊断监测手段在临床肿瘤学有用。
In a previous work we showed for the first time that human tumor cells secrete Hsp60 via exosomes, which are considered immunologically active microvesicles involved in tumor progression. This finding raised questions concerning the route followed by Hsp60 to reach the exosomes, its location in them, and whether Hsp60 can be secreted also via other mechanisms, e.g., by the Golgi. We addressed these issues in the work presented here. We found that Hsp60 localizes in the tumor cell plasma membrane, is associated with lipid rafts, and ends up in the exosomal membrane. We also found evidence that Hsp60 localizes in the Golgi apparatus and its secretion is prevented by an inhibitor of this organelle. We propose a multistage process for the translocation of Hsp60 from the inside to the outside of the cell that includes a combination of protein traffic pathways and, ultimately, presence of the chaperonin in the circulating blood. The new information presented should help in designing future strategies for research and for developing diagnostic-monitoring means useful in clinical oncology.
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