He Liuqing, Chen Quan, Wu Xiaoying
Department of Pathology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, China.
Department of Pathology, School of Basic Medical Science, Central South University, Changsha, Hunan, 410013, China.
J Ovarian Res. 2025 Feb 15;18(1):28. doi: 10.1186/s13048-025-01616-3.
Tumour-associated macrophages (TAMs) are the most abundant immune cells in the tumour environment and are considered similar to M2 macrophages, which facilitate cancer progression. Exosomes, as important mediators of the cross-talk between tumour cells and tumour-associated macrophages, can facilitate the development and metastasis of ovarian cancer by mediating M2 macrophage polarization. However, the exact mechanisms underlying the communication between ovarian cancer (OC) cells and tumour-associated macrophages during OC progression remain unclear.
Here, we demonstrated that high expression of miR-205 was associated with M2 macrophage infiltration, which affected the prognosis of OC patients. Importantly, tumour-derived miR-205 could be transported from OC cells to macrophages via exosomes and promote cancer cell invasion and metastasis by inducing M2-like macrophage polarization. Animal experiments further confirmed that exosomal miR-205-induced M2 macrophages accelerated OC progression in vivo. Mechanistically, miR-205 downregulated PTEN, activating the PI3K/AKT/mTOR signalling pathway, which is critical for M2 polarization.
These results reveal that exosomal miR-205 plays a pivotal role in macrophage polarization within the OC microenvironment, highlighting its potential as a therapeutic target for OC treatment. This study not only enhances our understanding of the interactions between tumour and immune cells but also opens new avenues for targeted therapies against exosomal miR-205 in ovarian cancer.
肿瘤相关巨噬细胞（TAMs）是肿瘤微环境中最丰富的免疫细胞，被认为类似于促进癌症进展的M2巨噬细胞。外泌体作为肿瘤细胞与肿瘤相关巨噬细胞之间相互作用的重要介质，可通过介导M2巨噬细胞极化促进卵巢癌的发展和转移。然而，在卵巢癌（OC）进展过程中，OC细胞与肿瘤相关巨噬细胞之间通讯的确切机制仍不清楚。
在此，我们证明miR-205的高表达与M2巨噬细胞浸润相关，这影响了OC患者的预后。重要的是，肿瘤来源的miR-205可通过外泌体从OC细胞转运至巨噬细胞，并通过诱导M2样巨噬细胞极化促进癌细胞的侵袭和转移。动物实验进一步证实，外泌体miR-205诱导的M2巨噬细胞在体内加速了OC进展。机制上，miR-205下调PTEN，激活对M2极化至关重要的PI3K/AKT/mTOR信号通路。
这些结果表明，外泌体miR-205在OC微环境中的巨噬细胞极化中起关键作用，突出了其作为OC治疗靶点的潜力。本研究不仅增强了我们对肿瘤与免疫细胞之间相互作用的理解，也为针对卵巢癌中外泌体miR-205的靶向治疗开辟了新途径。
