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Cancer cell exosomes can initiate malignant cell transformation

Karoliina Stefanius, Kelly A. Servage, Marcela de Souza Santos, Jason Toombs, Hillery Fields Gray, Suneeta Chimalapati, Min S. Kim, View ORCID ProfileRolf A. Brekken, View ORCID ProfileKim Orth
doi: https://doi.org/10.1101/360982
Karoliina Stefanius
1Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
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Kelly A. Servage
1Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
2Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
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Marcela de Souza Santos
1Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
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Jason Toombs
3Division of Surgical Oncology, Department of Surgery, Hamon Center for Therapeutic Oncology Research, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
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Hillery Fields Gray
1Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
2Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
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Suneeta Chimalapati
1Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
2Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
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Min S. Kim
5Center for Bioinformatics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
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Rolf A. Brekken
3Division of Surgical Oncology, Department of Surgery, Hamon Center for Therapeutic Oncology Research, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
4Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
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  • ORCID record for Rolf A. Brekken
Kim Orth
1Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
2Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
6Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
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  • ORCID record for Kim Orth
  • For correspondence: Kim.Orth@utsouthwestern.edu
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Abstract

Cancer evolves through a multistep process that occurs by the temporal accumulation of genetic mutations mediated by intracellular and extracellular cues. We observe that exosomes isolated from pancreatic cancer cells, but not normal pancreatic cells, can initiate the first step of malignant cell transformation. Injection of exosome-initiated transformed cells into mice results in aggressive tumor growth. Using proteomic profiling and DNA sequencing of exosome-treated and transformed cells, we show that cancer cell exosomes act as a classic initiator by causing random genetic changes in recipient cells. Our studies provide new insight into a function of cancer cell exosomes and how they might specifically contribute to orchestrated local cell transformation.

One Sentence Summary Exosomes function as an initiator of tumor formation.

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Posted July 03, 2018.
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Cancer cell exosomes can initiate malignant cell transformation
Karoliina Stefanius, Kelly A. Servage, Marcela de Souza Santos, Jason Toombs, Hillery Fields Gray, Suneeta Chimalapati, Min S. Kim, Rolf A. Brekken, Kim Orth
bioRxiv 360982; doi: https://doi.org/10.1101/360982
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Cancer cell exosomes can initiate malignant cell transformation
Karoliina Stefanius, Kelly A. Servage, Marcela de Souza Santos, Jason Toombs, Hillery Fields Gray, Suneeta Chimalapati, Min S. Kim, Rolf A. Brekken, Kim Orth
bioRxiv 360982; doi: https://doi.org/10.1101/360982

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