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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监测癌症患者随访中的 HSP70 外泌体：一项临床前瞻性试点研究。


外泌体是血液中所有细胞释放的纳米囊泡。它们用作癌症潜在生物标志物的关键点是将肿瘤来源的外泌体与其他循环纳米囊泡区分开来。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。我们之前表明，来自癌细胞的外泌体在膜上携带 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点研究，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。我们发现循环外泌体 HSP70 水平（而非可溶性 HSP70）反映了肿瘤活检中的 HSP70 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 HSP70 外泌体水平与疾病状态相关，并且与循环肿瘤细胞相比，HSP70 外泌体水平是更敏感的肿瘤传播预测因子。最后，我们的案例研究表明，HSP70-外泌体水平与治疗反应呈负相关，因此，监测循环外泌体 HSP70 的变化可能有助于预测肿瘤反应和临床结果。