Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin 300052, China.
Tianjin Neurological Institute, Key Laboratory of Post-neurotrauma Neuro-repair and Regeneration in Central Nervous System, Ministry of Education and Tianjin City, Tianjin 300052, China.
Theranostics. 2020 May 17;10(15):6674-6694. doi: 10.7150/thno.45688. eCollection 2020.
: Intercellular communication via extracellular vesicles (EVs) plays a critical role in glioma progression. However, little is known about the precise mechanism regulating EV secretion and function. Our previous study revealed that Cavin1 was positively correlated with malignancy grades of glioma patients, and that overexpressing Cavin1 in glioma cells enhanced the malignancy of nearby glioma cells via EVs. : The current study used bioinformatics to design a variant Cavin1 (vCavin1) incapable of interacting with Caveolin1, and compared the effects of overexpressing Cavin1 and vCavin1 in glioma cells on EV production and function. : Remarkably, our results indicated that Cavin1 expression enhanced the secretion, uptake, and homing ability of glioma-derived EVs. EVs expressing Cavin1 promoted glioma growth and . In addition, Cavin1 expressing murine glioma cells recruited and activated microglia via EVs. However, vCavin1 neither was loaded onto EVs nor altered EV secretion and function. : Our findings suggested that Cavin1-Caveolin1 interaction played a significant role in regulating production and function of glioma-EVs, and may act as a promising therapeutic target in gliomas that express high levels of Cavin1.
细胞外囊泡（EVs）介导的细胞间通讯在胶质瘤进展中起着关键作用。然而，对于调控 EV 分泌和功能的确切机制知之甚少。我们之前的研究表明，Cavin1 与胶质瘤患者的恶性程度呈正相关，并且在胶质瘤细胞中过表达 Cavin1 通过 EV 增强了邻近胶质瘤细胞的恶性程度。本研究使用生物信息学设计了一种不能与 Cavéolin1 相互作用的 Cavin1 变体（vCavin1），并比较了过表达 Cavin1 和 vCavin1 在胶质瘤细胞中对 EV 产生和功能的影响。值得注意的是，我们的结果表明，Cavin1 表达增强了胶质瘤衍生 EV 的分泌、摄取和归巢能力。表达 Cavin1 的 EV 促进了胶质瘤的生长和侵袭。此外，表达 Cavin1 的鼠源性胶质瘤细胞通过 EV 招募并激活小胶质细胞。然而，vCavin1 既不能加载到 EV 上，也不能改变 EV 的分泌和功能。我们的研究结果表明，Cavin1-Caveolin1 相互作用在调节胶质瘤-EV 的产生和功能中起重要作用，并且可能成为表达高水平 Cavin1 的胶质瘤的有前途的治疗靶点。
