Cancer cells copy migratory behavior and exchange signaling networks via extracellular vesicles.
Sander C SteenbeekThang V PhamJoep de LigtAnoek ZomerJaco C KnolSander R PiersmaTim SchelfhorstRick HuisjesRaymond M SchiffelersEdwin CuppenConnie R JiménezJacco van RheenenPublished in: The EMBO journal (2018)
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.
Keyphrases
- squamous cell carcinoma
- small cell lung cancer
- tandem mass spectrometry
- induced apoptosis
- cell migration
- cell cycle arrest
- single cell
- ultra high performance liquid chromatography
- high resolution
- liquid chromatography
- simultaneous determination
- high performance liquid chromatography
- single molecule
- endoplasmic reticulum stress
- oxidative stress
- cell death
- risk assessment
- human health
- optical coherence tomography
- skin cancer
- climate change
- solid phase extraction