TY - JOUR
T1 - Cancer cells copy migratory behavior and exchange signaling networks via extracellular vesicles
AU - Steenbeek, Sander C.
AU - Pham, Thang V.
AU - de Ligt, Joep
AU - Zomer, Anoek
AU - Knol, Jaco C.
AU - Piersma, Sander R.
AU - Schelfhorst, Tim
AU - Huisjes, Rick
AU - Schiffelers, Raymond M.
AU - Cuppen, Edwin
AU - Jimenez, Connie R.
AU - van Rheenen, Jacco
PY - 2018
Y1 - 2018
N2 - 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 RNAs, and many of these biomolecules are from interconnected signaling networks involved in cellular processes such as migration. Thus, EVs contain numerous proteins and RNAs and act on recipient cells by invoking a multi-faceted biological response including cell migration.
AB - 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 RNAs, and many of these biomolecules are from interconnected signaling networks involved in cellular processes such as migration. Thus, EVs contain numerous proteins and RNAs and act on recipient cells by invoking a multi-faceted biological response including cell migration.
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85050959858&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/29907695
U2 - https://doi.org/10.15252/embj.201798357
DO - https://doi.org/10.15252/embj.201798357
M3 - Article
C2 - 29907695
SN - 0261-4189
VL - 37
JO - EMBO Journal
JF - EMBO Journal
IS - 15
M1 - e98357
ER -