title: Mast cell exosomes promote lung adenocarcinoma cell proliferation - role of KIT-stem cell factor signaling.
abstract: BACKGROUND
  Human cells release nano-sized vesicles called exosomes, containing mRNA, miRNA and specific proteins. Exosomes from one cell can be taken up by another cell, which is a recently discovered cell-to-cell communication mechanism. Also, exosomes can be taken up by different types of cancer cells, but the potential functional effects of mast cell exosomes on tumor cells remain unknown.
  
  
  RESULTS
  Exosomes were isolated from the human mast cell line, HMC-1, and uptake of PKH67-labelled exosomes by the lung epithelial cell line, A549, was examined using flow cytometry and fluorescence microscopy. The RNA cargo of the exosomes was analyzed with a Bioanalyzer and absence or presence of the c-KIT mRNA was determined by RT-PCR. The cell proliferation was determined in a BrdU incorporation assay, and proteins in the KIT-SCF signaling pathway were detected by Western blot. Our result demonstrates that exosomes from mast cells can be taken up by lung cancer cells. Furthermore, HMC-1 exosomes contain and transfer KIT protein, but not the c-KIT mRNA to A549 cells and subsequently activate KIT-SCF signal transduction, which increase cyclin D1 expression and accelerate the proliferation in the human lung adenocarcinoma cells.
  
  
  CONCLUSIONS
  Our results indicate that exosomes can transfer KIT as a protein to tumor cells, which can affect recipient cell signaling events through receptor-ligand interactions.
authors.forename: Hui
authors.initials: H
authors.lastname: Xiao
authors.forename: Cecilia
authors.initials: C
authors.lastname: Lässer
authors.forename: Ganesh Vilas
authors.initials: GV
authors.lastname: Shelke
authors.forename: Juan
authors.initials: J
authors.lastname: Wang
authors.forename: Madeleine
authors.initials: M
authors.lastname: Rådinger
authors.forename: Taral Rameshchand
authors.initials: TR
authors.lastname: Lunavat
authors.forename: Carina
authors.initials: C
authors.lastname: Malmhäll
authors.forename: Li Hui
authors.initials: LH
authors.lastname: Lin
authors.forename: Jia
authors.initials: J
authors.lastname: Li
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.forename: Jan
authors.initials: J
authors.lastname: Lötvall
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology*; D000077192:Adenocarcinoma of Lung; D000818:Animals; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D019938:Cyclin D1 / Q000378:metabolism; D055354:Exosomes / Q000378:metabolism*; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology*; D008407:Mast Cells / Q000378:metabolism*; D051379:Mice; D041681:NIH 3T3 Cells; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D021381:Protein Transport; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction
chemical_list: C530104:CCND1 protein, human; D012333:RNA, Messenger; D019938:Cyclin D1; D019869:Phosphatidylinositol 3-Kinases; D019009:Proto-Oncogene Proteins c-kit