Migration Of Human Adipose-derived Mesenchymal Stem Cells Exosomes For Breast Cancer Cell Lines

Exosomes are40-100nm diameter vesicles that are secreted upon fusion of multivesicular endosomes with the plasma membrane. Exosomes contain not only membrane components, but also nucleic acids, which can be transferred to other cells where they remain functional. Lots of researches have showed exosomes have functions in fields ranging from immunology to neurobiology and tumor biology, as well as potential clinical applications, such as biomarkers or as therapeutic tools.In the first part, we investigated the influence of MSC-derived exosomes on breast cancer cells. Breast cancer is the most frequent malignancy among women, which is the leading cause of cancer-related death in women worldwide. Human mesenchymal stem cell (MSC)-conditioned medium (CM) was previously reported to affect the biology of tumor cells, however the precise mechanisms remain unclear. Here we show that MSCs secreted40-to100-nm particles which have typical characteristics of exosomes and these MSC-derived exosomes could promote migration of breast cancer cell line MCF7. Global gene expression profiling revealed that several cancer-related signaling pathways were upregulated after exosome treatment in MCF7and the Wnt signaling pathway was further confirmed to be activated. Our findings demonstrated a new mechanism through which MSC-CM may contribute to tumor cell migration.In the second part of this study, we studied the conversion of ESCs to NSCs in vitro. In the serum-free medium, firstly, we induced ESCs to neuroepithelial progenitor cells (NPCs). Then, NPCs were cultured in a suspension medium supplemented with EGF and FGF2and aggregates into multicellular structure to differentiate to neural stem cells (NSCs). We used46C for monitoring and quantitating the transition from ESCs to NPCs. Dynamic expression of NSCs marker was determined by quantitative PCR and immunoflurescence. After5days of induction, mESCs showed high expression of Soxl+and formed the rosette structure.3days later we harvested the large aggregates and trypsinise into single cell suspension to replate. The majority of cell aggregates would settle and become bipolar cells in7days. As determined by real-time quantitative PCR (qPCR), Pax6、Nestin、Mash1、BLBP (FabP7) genes expressed highly in NSCs. The immunoflurescence demonstrated the expression of Nestin+、RC2+、Pax6+. Consequently, ESCs can successfully be induced to NSCs, and NSCs have the capacity of maintaining self-renewal status in vitro.