Abstract
Insulinoma is an excessive insulin-released beta cell tumor. Pancreas cancer is one of the deadliest malignant neoplasms. Exosomes are secreted cell membrane vesicles containing a large number of proteins, lipids, and nucleic acids. The aim of this study is to investigate the effects of exosomes on two cell lines of benign and malignant character. For the first time, exosomes were isolated from pancreatic island-derived progenitor cells (PID-PCs) and applied to INS-1 and MiaPaCa-2 cells. In addition, exosomes isolated from PID-PC, MiaPaca-2, and INS-1 cells were characterized in order to compare their sizes with other previously isolated exosomes. Alix, TSG101, CD9, and CD81 were analyzed. The size and concentration of exosomes and the cell viability were detected. The cells were marked with HSP90, HSF-1, Kaspaz-8, Active-Kaspaz-3, Beclin, and p-Bcl-2. The cell cytotoxicity and insulin levels kit were measured. Alix in all exosomes, and PID-PC, MiaPaca-2 cell lysates; TSG101 in PID-PC and MiaPaca-2 cell lysates; CD9 in INS-1 exosomes were detected. The dimensions of isolated exosomes were 103.6 ± 28.6 nm, 100.7 ± 10 nm, and 147.2 ± 12.3 nm for PID-PCs, MiaPaca-2, and INS-1 cells. The cell viability decreased and HSP90 increased in the MiaPaca-2 cells. The HSF-1 was higher in the control MiaPaca-2 cell compared to the control INS-1 cell, and the exosome-treated MiaPaca-2 cell compared to the exosome-treated INS-1 cell. Beclin and p-Bcl-2 were decreased in the exosome-treated MiaPaca-2 cells. The insulin level in the cell lysates increased compared to cell secretion in INS-1 cells. In conclusion, exosomes isolated from the PID-PC caused cell death in the MiaPaca-2 cells in a time- and dose-dependent manner. The IC50 value determined for MiaPaca-2 cells has no effect on cell viability in INS-1 cells, which best mimics pancreatic beta cells and can be used instead of healthy pancreatic beta cells. Isolated exosomes can kill cancer cells without damaging healthy cells.
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The data generated during the current study are available from the corresponding author upon reasonable request.
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Acknowledgements
The authors would like to thank Prof. Dr. Claes B. Wollheim (University Medical Center, Geneva) for providing the kind gift of insulinoma INS-1 cell lines. We would like to thank Istanbul University Scientific Research Project Coordination Unit. Simple Wes device, purchased by Istanbul University Scientific Research Project Coordination Unit with project number 32156, was used.
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This work was supported by the Scientific Research Project Coordination Unit of Istanbul University (project no: 37205).
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Imren Hasoglu, contributed to creating the main idea, did all experiments, and wrote the manuscript. Ayse Karatug Kacar, created the main idea and experimental design, organized experiments, analyzed and evaluation of experimental results contributed to writing the manuscript, editing the manuscript.
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Hasoglu, I., Karatug Kacar, A. The therapeutic effects of exosomes the first time isolated from pancreatic islet-derived progenitor cells in the treatment of pancreatic cancer. Protoplasma 261, 281–291 (2024). https://doi.org/10.1007/s00709-023-01896-w
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DOI: https://doi.org/10.1007/s00709-023-01896-w