Dipartimento BIONEC, Sezione di Anatomia Umana, University of Palermo, Palermo, Italy.
PLoS One. 2012;7(7):e42008. doi: 10.1371/journal.pone.0042008. Epub 2012 Jul 25.
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.
CONCLUSIONS/SIGNIFICANCE: 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.
在之前的一项研究中，我们首次发现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具有免疫活性的微小囊泡。这一发现引发了一些问题，即 HSP60 到达外泌体的途径、其在其中的位置，以及 HSP60 是否还可以通过其他途径分泌，例如通过高尔基体。我们在本研究中解决了这些问题。
我们发现 HSP60 定位于肿瘤细胞膜，与脂筏相关，并最终定位于外泌体膜。我们还发现证据表明 HSP60 定位于高尔基体，其分泌被该细胞器的抑制剂所阻止。
结论/意义：我们提出了 HSP60 从细胞内到细胞外的易位的多阶段过程，该过程包括蛋白质运输途径的组合，最终 HSP60 存在于循环血液中。所呈现的新信息应有助于设计未来的研究策略，并开发对临床肿瘤学有用的诊断监测手段。
