PT  - JOURNAL ARTICLE
AU  - Karoliina Stefanius
AU  - Kelly A. Servage
AU  - Marcela de Souza Santos
AU  - Jason Toombs
AU  - Hillery Fields Gray
AU  - Suneeta Chimalapati
AU  - Min S. Kim
AU  - Rolf A. Brekken
AU  - Kim Orth
TI  - Cancer cell exosomes can initiate malignant cell transformation
AID  - 10.1101/360982
DP  - 2018 Jan 01
TA  - bioRxiv
PG  - 360982
4099  - http://biorxiv.org/content/early/2018/07/03/360982.short
4100  - http://biorxiv.org/content/early/2018/07/03/360982.full
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.