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

doi:10.1101/360982

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

Research output: Contribution to journal › Article › peer-review

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.

Original language	English (US)
Journal	Unknown Journal
DOIs	https://doi.org/10.1101/360982
State	Published - Jul 3 2018

ASJC Scopus subject areas

Biochemistry, Genetics and Molecular Biology(all)
Agricultural and Biological Sciences(all)
Immunology and Microbiology(all)
Neuroscience(all)
Pharmacology, Toxicology and Pharmaceutics(all)

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10.1101/360982

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title = "Cancer cell exosomes can initiate malignant cell transformation",

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.",

author = "Karoliina Stefanius and Servage, {Kelly A.} and {de Souza Santos}, Marcela and Jason Toombs and Gray, {Hillery Fields} and Suneeta Chimalapati and Kim, {Min S.} and Brekken, {Rolf A.} and Kim Orth",

note = "Publisher Copyright: The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission. Copyright: Copyright 2020 Elsevier B.V., All rights reserved.",

year = "2018",

month = jul,

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doi = "10.1101/360982",

language = "English (US)",

journal = "Seminars in Fetal and Neonatal Medicine",

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T1 - Cancer cell exosomes can initiate malignant cell transformation

AU - Stefanius, Karoliina

AU - Servage, Kelly A.

AU - de Souza Santos, Marcela

AU - Toombs, Jason

AU - Gray, Hillery Fields

AU - Chimalapati, Suneeta

AU - Kim, Min S.

AU - Brekken, Rolf A.

AU - Orth, Kim

N1 - Publisher Copyright: The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission. Copyright: Copyright 2020 Elsevier B.V., All rights reserved.

PY - 2018/7/3

Y1 - 2018/7/3

N2 - 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.

AB - 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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