Mast cell exosomes promote lung adenocarcinoma cell proliferation – role of KIT-stem cell factor signaling

Cell Communication and Signaling

Research

Li Li¹  Juan Wang¹  Li Hui Lin¹  Jia Li¹  Hui Xiao²  Carina Malmhäll³  Taral Rameshchand Lunavat³  Cecilia Lässer³  Jan Lötvall³  Madeleine Rådinger³  Ganesh Vilas Shelke³ 

[1] Department of Laboratory Medicine, Shanghai First People’s Hospital, Shanghai Jiao Tong University, Shanghai, China;Department of Laboratory Medicine, Shanghai First People’s Hospital, Shanghai Jiao Tong University, Shanghai, China;Krefting Research Centre, Department of Internal Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden;Krefting Research Centre, Department of Internal Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden;

关键词: Exosomes;    Extracellular vesicles;    KIT;    Lung cancer;    Mast cell;    Transfer;   

DOI  :  10.1186/s12964-014-0064-8

 received in 2014-04-04, accepted in 2014-09-30,  发布年份 2014

来源: Springer

【 摘 要 】

BackgroundHuman 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.Methods and resultsExosomes 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.ConclusionsOur results indicate that exosomes can transfer KIT as a protein to tumor cells, which can affect recipient cell signaling events through receptor-ligand interactions.

【 授权许可】

Unknown   
© Xiao et al.; licensee Biomed Central Ltd. 2014. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.