Theranostics 2020; 10(15):6674-6694. doi:10.7150/thno.45688

Research Paper

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

Lin Wang1,2,*, Chao Yang1,2,*, Qixue Wang1,2, Qi Liu3, Yunfei Wang1,2, Junhu Zhou1,2, Yansheng Li1,2, Yanli Tan4,5,✉, Chunsheng Kang1,2,✉

1. Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin 300052, China;
2. 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;
3. State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Functional Polymer Materials of Ministry of Education, College of Chemistry, Nankai University, Tianjin 300071, China;
4. Department of Pathology, Affiliated Hospital of Hebei University, Baoding 071000, China;
5. Department of Pathology, Hebei University Medical College, Baoding 071000, China.
* These authors contributed equally to this work.

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Citation:
Wang L, Yang C, Wang Q, Liu Q, Wang Y, Zhou J, Li Y, Tan Y, Kang C. Homotrimer cavin1 interacts with caveolin1 to facilitate tumor growth and activate microglia through extracellular vesicles in glioma. Theranostics 2020; 10(15):6674-6694. doi:10.7150/thno.45688. Available from http://www.thno.org/v10p6674.htm

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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.

Keywords: Cavin1-Caveolin1 interaction, extracellular vesicles, glioma, microglia