Non-stem bladder cancer cell-derived extracellular vesicles promote cancer stem cell survival in response to chemotherapy.

Autor: Chung WM; Department of Urology, University of Rochester Medical Center, 601 Elmwood Ave, Box 656, Rochester, NY, 14642, USA., Molony RD; Department of Urology, University of Rochester Medical Center, 601 Elmwood Ave, Box 656, Rochester, NY, 14642, USA., Lee YF; Department of Urology, University of Rochester Medical Center, 601 Elmwood Ave, Box 656, Rochester, NY, 14642, USA. YiFen_Lee@URMC.Rochester.edu.; Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, NY, USA. YiFen_Lee@URMC.Rochester.edu.; Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, NY, USA. YiFen_Lee@URMC.Rochester.edu.
Jazyk: angličtina
Zdroj: Stem cell research & therapy [Stem Cell Res Ther] 2021 Oct 09; Vol. 12 (1), pp. 533. Date of Electronic Publication: 2021 Oct 09.
DOI: 10.1186/s13287-021-02600-6
Abstrakt: Background: Chemosenstive non-stem cancer cells (NSCCs) constitute the bulk of tumors and are considered as part of the cancer stem cell (CSC) niche in the tumor microenvironment (TME). Tumor-derived extracellular vesicles (EVs) mediate the communication between tumors and the TME. In this study, we sought to investigate the impacts of EVs released by NSCCs on the maintenance of CSC properties and chemoresistance.
Methods: We employed murine MB49 bladder cancer (BC) sub-lines representing CSCs and NSCCs as a model system. Chemotherapy drugs were used to treat NSCCs in order to collect conditioned EVs. The impacts of NSCC-derived EVs on CSC progression were evaluated through sphere formation, cytotoxicity, migration, and invasion assays, and by analyzing surface marker expression on these BC cells. Differential proteomic analyses were conducted to identify cargo protein candidates involved in the EV-mediated communication between NSCCs and CSCs.
Results: NSCC-derived EVs contained cargo proteins enriched in proteostasis-related functions, and significantly altered the development of CSCs such that they were more intrinsically chemoresistant, aggressive, and better able to undergo self-renewal.
Conclusions: We thus identified a novel communication mechanism whereby NSCC-EVs can alter the relative fitness of CSCs to promote disease progression and the acquisition of chemoresistance.
(© 2021. The Author(s).)
Databáze: MEDLINE
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