| Purpose The aim of this paper is to observe direct interaction between glioma stem cells(GSCs) and dendritic cells(DC) in vitro and investigate the possible mechanism of malignant transformation of dendritic cell.Methods Bone marrow cavity flushing cells from nude mice expressing enhanced green fluorescent protein(EGFP) were collected and cultured in medium favored for DC growth, then DCs were harvested and co-cultured with red fluorescent protein(RFP) transfected GSCs cell line SU3. After 10 days interaction between GSCs and DCs, EGFP/RFP double positive cells with high proliferation ability were monocloned. Identification of DC molecular markers, analysis of chromosome karyotype, colony formation assay, cell invasion assay and in vivo tumorigenesis ability assay were performed. Gene expression difference between normal mature DC and malignant transformed DCs were further analyzed.Results The malignant transformed DCs(t-DC) had no morphological changes when compared with typical dendritic cells. They expressed DCs cell surface markers such as CD11 c, CD80 and signal regulated protein alpha(SIRP-α). It also possessed the biological characteristics of transformed cell, such as high proliferation, strong invasion and in vivo tumorigenesis. The chromosome karyotype assay turned out to be murine heteroploid. Whole genome expression profile assay showed, if compared with normal DCs,malignant transformed DCs had 3734 different genes whose fold-change is above 3, including 2216 genes up-regulated and 1518 genes down-regulated. Further study showed that TAK1 and IGF1 protein of AKT-FOXO signal pathway played active roles in malignant transformation of DCs.Conclusion Glioma stem cells SU3 can induce malignant transformation of bone marrow derived dendritic cells in vitro. AKT-FOXO signal pathway may be involved in the malignant transformation of DCs. |
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