70-kDa Heat Shock Proteins (HSPA/HSP70) are chaperones playing a central role in the proteostasis control mechanisms. Their basal expression can be highly elevated as an adaptive response to environmental and pathophysiological stress conditions. HSPA2, one of poorly characterised chaperones of the HSPA/HSP70 family, has recently emerged as epithelial cells differentiation-related factor. It is also commonly expressed in cancer cells, where its functional significance remains unclear. Previously, we have found that proteotoxic stress provokes a decrease in HSPA2 levels in cancer cells. In the present study we found that proteasome inhibition-related loss of HSPA2 from cancer cells neither is related to a block in the gene transcription nor does it relate to increased autophagy-mediated disposals of the protein. Proteotoxic stress stimulated extracellular release of HSPA2 in extracellular vesicles (EVs). Interestingly, EVs containing HSPA2 are also released by non-stressed cancer and normal cells. In human urinary EVs levels of HSPA2 were correlated with the levels of TSG101, one of the main EVs markers. We conclude that HSPA2 may constitute basic components of EVs. Nevertheless, its specific role in EVs and cell-to-cell communication requires further investigation.

70-kDa 热休克蛋白 (HSPA/HSP70) 是在蛋白质稳态控制机制中发挥核心作用的伴侣。作为对环境和病理生理应激条件的适应性反应，它们的基础表达可以高度升高。HSPA2 是 HSPA/HSP70 家族中特征较差的伴侣蛋白之一，最近已成为上皮细胞分化相关因子。它也常在癌细胞中表达，但其功能意义尚不清楚。以前，我们发现蛋白毒性应激会导致癌细胞中 HSPA2 水平降低。在本研究中，我们发现癌细胞中与蛋白酶体抑制相关的 HSPA2 丢失既与基因转录阻断无关，也与自噬介导的蛋白质处理增加无关。蛋白毒性应激刺激细胞外囊泡 (EV) 中 HSPA2 的细胞外释放。有趣的是，含有 HSPA2 的 EV 也由非应激癌细胞和正常细胞释放。在人类尿液 EV 中，HSPA2 的水平与 TSG101 的水平相关，TSG101 是主要的 EV 标志物之一。我们得出结论，HSPA2 可能构成 EV 的基本组件。然而，它在 EV 和细胞间通讯中的具体作用需要进一步研究。