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In vivo-mimicking 3D cultures secrete distinct extracellular vesicles upon cancer cell invasion

Jens C. Luoto, Leila S. Coelho-Rato, Sara H. Bengs, Jannica Roininen, John E. Eriksson, View ORCID ProfileLea Sistonen, View ORCID ProfileEva Henriksson
doi: https://doi.org/10.1101/2020.12.22.423913
Jens C. Luoto
1Åbo Akademi University, Faculty of Science and Engineering, Turku, Finland
2Turku Bioscience Centre, University of Turku and Åbo Akademi University, Turku, Finland
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Leila S. Coelho-Rato
1Åbo Akademi University, Faculty of Science and Engineering, Turku, Finland
2Turku Bioscience Centre, University of Turku and Åbo Akademi University, Turku, Finland
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Sara H. Bengs
1Åbo Akademi University, Faculty of Science and Engineering, Turku, Finland
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Jannica Roininen
1Åbo Akademi University, Faculty of Science and Engineering, Turku, Finland
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John E. Eriksson
1Åbo Akademi University, Faculty of Science and Engineering, Turku, Finland
2Turku Bioscience Centre, University of Turku and Åbo Akademi University, Turku, Finland
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Lea Sistonen
1Åbo Akademi University, Faculty of Science and Engineering, Turku, Finland
2Turku Bioscience Centre, University of Turku and Åbo Akademi University, Turku, Finland
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Eva Henriksson
1Åbo Akademi University, Faculty of Science and Engineering, Turku, Finland
2Turku Bioscience Centre, University of Turku and Åbo Akademi University, Turku, Finland
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  • ORCID record for Eva Henriksson
  • For correspondence: eva.henriksson@abo.fi
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Abstract

Extracellular vesicles (EVs) loaded with biomolecules are important in intercellular communication and mediate local and long-range signals in cancer metastasis. However, it is currently unknown how the development of the primary tumor and onset of invasion affect the secretion and characteristics of EVs. In this study, we developed an EV production method utilizing in vivo-mimicking extracellular matrix-based 3D cultures, which allows tracking of EVs over the course of invasive development of tumor organoids. Using this method, combined with proteomic profiling, we show that PC3 human prostate cancer organoids secrete EVs with previously undefined protein cargo, which substantially differs from EV cargo of 2D cultured cells. Intriguingly, an increase in EV amounts and extensive changes in EV protein composition were detected upon invasive transition of the organoids. These results reveal that EV secretion and cargo loading are highly dependent on the developmental status of the tumor organoid, emphasizing the necessity of in vivo-mimicking conditions for discovery of novel cancer-derived EV components, applicable as diagnostic markers for cancer.

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Posted December 23, 2020.
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In vivo-mimicking 3D cultures secrete distinct extracellular vesicles upon cancer cell invasion
Jens C. Luoto, Leila S. Coelho-Rato, Sara H. Bengs, Jannica Roininen, John E. Eriksson, Lea Sistonen, Eva Henriksson
bioRxiv 2020.12.22.423913; doi: https://doi.org/10.1101/2020.12.22.423913
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In vivo-mimicking 3D cultures secrete distinct extracellular vesicles upon cancer cell invasion
Jens C. Luoto, Leila S. Coelho-Rato, Sara H. Bengs, Jannica Roininen, John E. Eriksson, Lea Sistonen, Eva Henriksson
bioRxiv 2020.12.22.423913; doi: https://doi.org/10.1101/2020.12.22.423913

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