A Small Vimentin-Binding Molecule Blocks Cancer Exosome Release and Reduces Cancer Cell Mobility
Autor: | Jianping Wu, Qian Xie, Yanjun Liu, Yanan Gao, Zhipeng Qu, Lian Mo, Ying Xu, Ruihuan Chen, Liyun Shi |
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Rok vydání: | 2021 |
Předmět: |
0301 basic medicine
small molecule Vimentin RM1-950 exosomes Exosome Metastasis 03 medical and health sciences vimentin 0302 clinical medicine medicine Pharmacology (medical) cancer mobility Tissue homeostasis Original Research Pharmacology biology Chemistry Cancer medicine.disease Microvesicles Cell biology inhibitor 030104 developmental biology 030220 oncology & carcinogenesis Cancer cell biology.protein Therapeutics. Pharmacology Intracellular |
Zdroj: | Frontiers in Pharmacology Frontiers in Pharmacology, Vol 12 (2021) |
ISSN: | 1663-9812 |
Popis: | Vimentin is an intermediate filament protein with diverse roles in health and disease far beyond its structural functions. Exosomes or small extracellular vesicles (sEVs) are key mediators for intercellular communication, contributing to tissue homeostasis and the progression of various diseases, especially the metastasis of cancers. In this study, we evaluated a novel vimentin-binding compound (R491) for its anti-cancer activities and its roles in cancer exosome release. The compound R491 induced a rapid and reversible intracellular vacuolization in various types of cancer cells. This phenotype did not result in an inhibition of cancer cell growth, which was consistent with our finding from a protein array that R491 did not reduce levels of major oncoproteins in cancer cells. Morphological and quantitative analyses on the intracellular vacuoles and extracellular exosomes revealed that in response to R491 treatment, the exosomes released from the cells were significantly reduced, while the exosomes retained as intra-luminal vesicles inside the cells were subsequently degraded. Vim+/− cells had lower amounts of vimentin and accordingly, lower amounts of both the retained and the released exosomes than Vim+/+ cells had, while the vimentin-binding compound R491 inhibited only the release of exosomes. Further functional tests showed that R491 significantly reduced the migration and invasion of cancer cells in vitro and decreased the amount of exosome in the blood in mice. Our study suggests that vimentin promotes exosome release, and small-molecule compounds that target vimentin are able to both block cancer exosome release and reduce cancer cell motility, and therefore could have potential applications for inhibiting cancer invasive growth. |
Databáze: | OpenAIRE |
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