Homotrimer cavin1 interacts with caveolin1 to facilitate tumor growth and activate microglia through extracellular vesicles in glioma.

ABSTRACT: Background: 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. Methods: 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. Results: Remarkably, our results indicated that Cavin1 expression enhanced the secretion, uptake, and homing ability of glioma-derived EVs. EVs expressing Cavin1 promoted glioma growth in vitro and in vivo. 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. Conclusion: 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.

SUBMITTER: Wang L 

PROVIDER: S-EPMC7295042 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature