Exosomes are nanovesicles released by all cells that can be found in the blood. A key point for their use as potential biomarkers in cancer is to differentiate tumour-derived exosomes from other circulating nanovesicles. Heat shock protein-70 (HSP70) has been shown to be abundantly expressed by cancer cells and to be associated with bad prognosis. We previously showed that exosomes derived from cancer cells carried HSP70 in the membrane while those from non-cancerous cells did not. In this work, we opened a prospective clinical pilot study including breast and lung cancer patients to determine whether it was possible to detect and quantify HSP70 exosomes in the blood of patients with solid cancers. We found that circulating exosomal HSP70 levels, but not soluble HSP70, reflected HSP70 content within the tumour biopsies. Circulating HSP70 exosomes increased in metastatic patients compared to non-metastatic patients or healthy volunteers. Further, we demonstrated that HSP70-exosome levels correlated with the disease status and, when compared with circulating tumour cells, were more sensitive tumour dissemination predictors. Finally, our case studies indicated that HSP70-exosome levels inversely correlated with response to the therapy and that, therefore, monitoring changes in circulating exosomal HSP70 might be useful to predict tumour response and clinical outcome.

中文翻译：

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在癌症患者的随访中监测HSP70外泌体：一项临床前瞻性先导研究。

外泌体是血液中所有细胞释放的纳米囊泡。用作癌症潜在生物标志物的关键点是区分肿瘤来源的外泌体与其他循环的纳米囊泡。热休克蛋白70（HSP70）已被证明在癌细胞中大量表达，并与不良预后相关。我们以前的研究表明，源自癌细胞的外泌体在膜中携带HSP70，而来自非癌细胞的外泌体则没有。在这项工作中，我们开展了一项包括乳腺癌和肺癌患者在内的前瞻性临床试验研究，以确定是否有可能检测和量化实体癌患者血液中的HSP70外泌体。我们发现循环的外泌体HSP70水平而非可溶性HSP70反映了肿瘤活检组织中HSP70的含量。与非转移患者或健康志愿者相比，转移患者的循环HSP70外泌体增加。此外，我们证明了HSP70-外泌体水平与疾病状况相关，并且与循环中的肿瘤细胞相比，是更敏感的肿瘤扩散预测因子。最后，我们的案例研究表明，HSP70外泌体水平与对治疗的反应呈负相关，因此，监测循环外泌体HSP70的变化可能对预测肿瘤反应和临床结果有用。