title: Fusion of cancer stem cells and mesenchymal stem cells contributes to glioma neovascularization.
abstract: The ability of tumor cells to autonomously generate tumor vessels has received considerable attention in recent years. However, the degree of autonomy is relative. Meanwhile, the effect of bone marrow-derived mesenchymal stem cells (BMSCs) on tumor neovascularization has not been fully elucidated. The present study aimed to illuminate whether cell fusion between glioma stem cells and BMSC is involved in glioma neovascularization. BMSCs were isolated from transgenic nude mice, of which all nucleated cells express green fluorescent protein (GFP). The immunophenotype and multilineage differentiation potential of BMSC were confirmed. SU3 glioma stem/progenitor cells were transfected with red fluorescent protein (SU3-RFP cells). In a co-culture system of BMSC-GFP and SU3-RFP, RFP+/GFP+ cells were detected and isolated by dual colors using FACS. The angiogenic effect of RFP+/GFP+ cells was determined in vivo and in vitro. Flow cytometry analysis showed that BMSC expressed high levels of CD105, C44, and very low levels of CD45 and CD11b. When co-cultured with SU3-RFP, 73.8% of cells co-expressing RFP and GFP were identified as fused cells in the 5th generation. The fused cells exhibited tube formation ability in vitro and could give rise to a solid tumor and form tumor blood vessels in vivo. In the dual-color orthotopic model of transplantable xenograft glioma, yellow vessel-like structures that expressed CD105, RFP and GFP were identified as de novo-formed vessels derived from the fused cells. The yellow vessels observed in the tumor-bearing mice directly arose from the fusion of BMSCs and SU3-RFP cells. Thus, cell fusion is one of the driving factors for tumor neovascularization.
authors.affiliation: Department of Neurosurgery, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215000, P.R. China.
authors.forename: Chao
authors.initials: C
authors.lastname: Sun
authors.affiliation: Department of Neurosurgery, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215000, P.R. China.
authors.forename: Dongliang
authors.initials: D
authors.lastname: Zhao
authors.affiliation: Department of Neurosurgery, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215000, P.R. China.
authors.forename: Xingliang
authors.initials: X
authors.lastname: Dai
authors.affiliation: Department of Neurosurgery, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215000, P.R. China.
authors.forename: Jinsheng
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Neurosurgery, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215000, P.R. China.
authors.forename: Xiaoci
authors.initials: X
authors.lastname: Rong
authors.affiliation: Department of Neurosurgery, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215000, P.R. China.
authors.forename: Haiyang
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215000, P.R. China.
authors.forename: Aidong
authors.initials: A
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215000, P.R. China.
authors.forename: Ming
authors.initials: M
authors.lastname: Li
authors.affiliation: Department of Neurosurgery, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215000, P.R. China.
authors.forename: Jun
authors.initials: J
authors.lastname: Dong
authors.affiliation: Department of Neurosurgery, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215000, P.R. China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Huang
authors.affiliation: Department of Neurosurgery, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215000, P.R. China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Lan
mesh_terms: D000818:Animals; D002459:Cell Fusion; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D018920:Coculture Techniques; D005910:Glioma / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D006822:Hybrid Cells / Q000637:transplantation*; D059630:Mesenchymal Stem Cells / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008819:Mice, Nude; D008822:Mice, Transgenic; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000502:physiology*; D014183:Transplantation, Heterologous