1.Tumor angiogenesis promoted by fusion of glioma stem/progenitor cells with bone marrow mesenchymal stem cells.
Dongliang ZHAO ; Xingliang DAI ; Chao SUN ; Jinsheng CHEN ; Xiaoci RONG ; Haiyang WANG ; Qilong WANG ; Qin RUI ; Aidong WANG ; Zhongyong WANG ; Jun DONG ; Qing LAN ; Qiang HUANG
Chinese Journal of Oncology 2015;37(5):336-341
OBJECTIVEThe aim of this study was to clarify whether the fusion of bone marrow mesenchymal stem cells (MSCs) with tumor cells can promote tumor angiogensis.
METHODSHuman glioma stem/progenitor cells (GSPCs) (SU3 cells) were transfected with red fluorescent protein (RFP) gene. Bone marrow mesenchymal stem cells (MSCs) were harvested from nude mice with whole-body green fluorescent protein (GFP) gene expression. Then the two kinds of cells were co-cultured in vitro. At the same time SU3-RFP was transplanted into the brain of GFP-expressing nude mice to establish xenograft tumors. The co-cultured cells, GFP/RFP double positive (yellow) cells and blood vessels obtained from the xenograft tumors were observed under fluorescent microscope and laser scanning confocal microscope.
RESULTSAfter five passages in vitro, MSCs maintained the proliferative activity and highly expressed CD105. CD105 was also expressed in the femurs of GFP-expressing nude mice, tumor cells, blood vessels of SU3 xenograft tumors, and clinical malignant gliomas. When MSCs were co-cultured with SU3-RFP, the ratio of yellow cells co-expressing RFP and GFP was significantly increased after extended time and continuous passages. According to the flow cytometry, yellow cells co-expressing RFP and GFP were 83.7% of the cultured cells. In tissue slices of the xenograft tumors, bundles of yellow vessel-like structure and cross-sectioned yellow vascular wall structures including vascular wall stroma cells were observed with RFP and GFP expression, and were identified as de novo formed vessels derived from fusion of MSCs with SU3-RFP cells.
CONCLUSIONCell fusion occurs between tumor cells and host MSCs and it promotes tumor angiogenesis.
Animals ; Bone Marrow Cells ; physiology ; Cell Communication ; Cell Fusion ; Cells, Cultured ; Glioma ; Green Fluorescent Proteins ; Humans ; Luminescent Proteins ; Mesenchymal Stromal Cells ; Mice ; Mice, Nude ; Microscopy, Fluorescence ; Neoplasms ; Neovascularization, Pathologic ; Stem Cells ; Transfection ; Transplantation, Heterologous