Cancer cell derived exosomes play important roles in cancer progression and modulation of the tumour microenvironment. This study aims to investigate the role of prokineticin receptor 1 (PKR1) positive exosomes on angiogenesis. In the present study, PKR1 expression in tumour samples from ovarian cancer patients were examined firstly. Then, two ovarian cancer cell lines, namely A2780 and HO‐8910 cells, were used to isolate and obtain the PKR1 positive exosomes from the serum free medium. The function analysis of PKR1 positive exosomes on angiogenesis was conducted by cell proliferation and migration assay, tube formation analysis, and tumour volume assay. The results showed that PKR1 expression was down regulated in tumour samples of ovarian cancer patients compared with adjacent normal tissues. The intracellular expression of PKR1 could be detected in A2780 and HO‐8910 cells. And, the isolated exosomes from the serum free medium were confirmed by transmission electron microscopic and NTA analysis, as well as the co‐presence of PKR1 with exosome marker CD63. The function analysis of PKR1 positive exosomes on angiogenesis demonstrated the uptake of PKR1 positive exosomes by human umbilical vein endothelial cells through immunofluorescence staining. The angiogenesis assays in vitro indicated that PKR1 positive exosomes promoted migration and tube formation of HUVECs but not proliferation. The endogenous PKR1 was also verified to help to enhance migration and promote tube formation of vascular endothelial cells, which might involved in the phosphorylation of STAT3. Additionally, The tumour volume from exosomes treated A2780 tumour‐bearing mice was significantly increased compared with the control group, accompanied with the induced PKR1 expression and phosphorylation of STAT3 level.

中文翻译：

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卵巢癌衍生的PKR1阳性外泌体通过促进体外迁移和管形成来促进血管生成

癌细胞衍生的外来体在癌症进展和肿瘤微环境的调节中起重要作用。这项研究旨在调查促动素受体1（PKR1）阳性外泌体在血管生成中的作用。在本研究中，首先检查了卵巢癌患者肿瘤样本中的PKR1表达。然后，使用两种卵巢癌细胞系，即A2780和HO-8910细胞，从无血清培养基中分离并获得PKR1阳性外泌体。通过细胞增殖和迁移测定，管形成分析和肿瘤体积测定进行PKR1阳性外泌体对血管生成的功能分析。结果表明，与邻近的正常组织相比，卵巢癌患者肿瘤样本中的PKR1表达下调。PKR1的细胞内表达可以在A2780和HO-8910细胞中检测到。并且，通过透射电子显微镜和NTA分析，以及PKR1与外泌体标记CD63的共存，证实了从无血清培养基中分离出的外泌体。PKR1阳性外泌体对血管生成的功能分析表明，人脐静脉内皮细胞通过免疫荧光染色吸收了PKR1阳性外泌体。体外血管生成测定表明，PKR1阳性外来体促进了HUVEC的迁移和管形成，但不促进增殖。还证实了内源性PKR1有助于增强迁移并促进血管内皮细胞的管形成，这可能与STAT3的磷酸化有关。此外，