The communication between tumor-derived exosomes and macrophages plays an important role in facilitating the progression of tumors. However, the regulatory mechanisms by which exosomes regulate tumor progression in esophageal squamous cell carcinoma (ESCC) have not been fully elucidated. We constructed a coculture system containing an ESCC cell line and macrophages using a Transwell chamber. We isolated exosomes from the conditioned medium of cancer cells, and characterized them with transmission electron microscopy and western blotting and used then to treat macrophages. We used co-immunoprecipitation to evaluate the interaction between hyaluronidase 1 (HYAL1) and Aurora B kinase (AURKB). We evaluated HYAL1 and AURKB expression in tissues and cells with quantitative reverse-transcription polymerase chain reaction (RT-qPCR) and western blotting. We used RT-qPCR, enzyme-linked immunosorbent assay (ELISA) and flow cytometry to detect macrophage polarization. We assessed cell viability, invasion and migration with the cell counting kit-8 (CCK-8), Transwell and wound healing assays. HYAL1 was highly expressed in ESCC tissues and cells and cancer cell-derived exosomes, and exosomes can be delivered to macrophages through the cancer cell-derived exosomes. The exosomes extracted from HYAL1-overexpressed ESCC cells suppressed M1 macrophage polarization and induced M2 macrophage polarization, thereby promoting ESCC cell viability, invasion and migration. HYAL1 silencing in ESCC cells produced the opposite effects on macrophage polarization and cancer cell functions. We found that HYAL1 interacted with AURKB and further activated the phosphoinositide 3-kinase (PI3K)/AKT signaling pathway in macrophages. In conclusion, ESCC-derived exosomes containing HYAL1 facilitate M2 macrophage polarization by targeting AURKB to active the PI3K/AKT signaling pathway, which in turn promotes ESCC progression.

中文翻译：

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肿瘤源性外泌体透明质酸酶1诱导M2巨噬细胞极化并促进食管癌进展

肿瘤来源的外泌体和巨噬细胞之间的通讯在促进肿瘤的进展中发挥着重要作用。然而，外泌体调节食管鳞状细胞癌（ESCC）肿瘤进展的调节机制尚未完全阐明。我们使用 Transwell 室构建了包含 ESCC 细胞系和巨噬细胞的共培养系统。我们从癌细胞的条件培养基中分离出外泌体，并通过透射电子显微镜和蛋白质印迹对其进行表征，然后用于治疗巨噬细胞。我们使用免疫共沉淀来评估透明质酸酶 1 (HYAL1) 和 Aurora B 激酶 (AURKB) 之间的相互作用。我们通过定量逆转录聚合酶链反应 (RT-qPCR) 和蛋白质印迹评估了组织和细胞中 HYAL1 和 AURKB 的表达。我们使用 RT-qPCR、酶联免疫吸附测定 (ELISA) 和流式细胞术来检测巨噬细胞极化。我们使用细胞计数试剂盒 8 (CCK-8)、Transwell 和伤口愈合检测评估了细胞活力、侵袭和迁移。HYAL1在ESCC组织和细胞以及癌细胞来源的外泌体中高表达，并且外泌体可以通过癌细胞来源的外泌体递送至巨噬细胞。从过度表达 HYAL1 的 ESCC 细胞中提取的外泌体抑制 M1 巨噬细胞极化并诱导 M2 巨噬细胞极化，从而促进 ESCC 细胞的活力、侵袭和迁移。ESCC 细胞中的 HYAL1 沉默对巨噬细胞极化和癌细胞功能产生相反的影响。我们发现HYAL1与AURKB相互作用并进一步激活巨噬细胞中的磷酸肌醇3激酶（PI3K）/AKT信号通路。总之，含有 HYAL1 的 ESCC 衍生外泌体通过靶向 AURKB 激活 PI3K/AKT 信号通路，促进 M2 巨噬细胞极化，进而促进 ESCC 进展。