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Cancer cells copy migratory behavior and exchange signaling networks via extracellular vesicles
Author(s) -
Steenbeek Sander C,
Pham Thang V,
Ligt Joep,
Zomer Anoek,
Knol Jaco C,
Piersma Sander R,
Schelfhorst Tim,
Huisjes Rick,
Schiffelers Raymond M,
Cuppen Edwin,
Jimenez Connie R,
Rheenen Jacco
Publication year - 2018
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.15252/embj.201798357
Subject(s) - biology , extracellular vesicles , microbiology and biotechnology , extracellular , signal transduction , cell signaling
Recent data showed that cancer cells from different tumor subtypes with distinct metastatic potential influence each other's metastatic behavior by exchanging biomolecules through extracellular vesicles (EVs). However, it is debated how small amounts of cargo can mediate this effect, especially in tumors where all cells are from one subtype, and only subtle molecular differences drive metastatic heterogeneity. To study this, we have characterized the content of EVs shed in vivo by two clones of melanoma (B16) tumors with distinct metastatic potential. Using the Cre‐LoxP system and intravital microscopy, we show that cells from these distinct clones phenocopy their migratory behavior through EV exchange. By tandem mass spectrometry and RNA sequencing, we show that EVs shed by these clones into the tumor microenvironment contain thousands of different proteins and RNA s, and many of these biomolecules are from interconnected signaling networks involved in cellular processes such as migration. Thus, EVs contain numerous proteins and RNA s and act on recipient cells by invoking a multi‐faceted biological response including cell migration.