Cancer cell exosomes can initiate malignant cell transformation

Author:

Stefanius Karoliina,Servage Kelly A.,de Souza Santos Marcela,Toombs Jason,Gray Hillery Fields,Chimalapati Suneeta,Kim Min S.,Brekken Rolf A.ORCID,Orth KimORCID

Abstract

AbstractCancer 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 SummaryExosomes function as aninitiatorof tumor formation.

Publisher

Cold Spring Harbor Laboratory

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