title: Establishment of a green fluorescent protein tracing murine model focused on the functions of host components in necrosis repair and the niche of subcutaneously implanted glioma.
abstract: Due to progress in the research of glioma stem cells and the glioma niche, development of an animal model that facilitates the elucidation of the roles of the host tissue and cells is necessary. The aim of the present study was to develop a subcutaneous xenograft green fluorescent protein nude mouse model and use this model to analyze the roles of host cells in tumor necrosis repair. Tumors derived from the human glioma stem/progenitor cell line SU3 were subcutaneously implanted in green fluorescent protein nude mice. The implanted tumors were then passed from animal to animal for 10 generations. Finally, subcutaneous xenografts were assayed with traditional pathology, immunopathological techniques and fluorescence photography. For each generation, the tumorigenicity rate was 100%. Subcutaneous xenografts were rich in blood vessels, and necrotic and hemorrhagic foci, which highly expressed hypoxia-inducible factor-1α, tumor necrosis factor, Ki-67, CD68 and CD11b. In the interstitial tissue, particularly in old hemorrhagic foci, there were numerous cells expressing green fluorescent protein, CD68 and CD11b. Green fluorescent protein nude mouse subcutaneous xenografts not only consistently maintained the high invasiveness and tumorigenicity of glioma stem/progenitor cells, but also consisted of a high concentration of tumor blood vessels and necrotic and hemorrhagic foci. Subcutaneous xenografts also expressed high levels of tumor microenvironment-related proteins and host-derived tumor interstitial molecules. The model has significant potential for further research on tumor tissue remodeling and the tumor microenvironment.
authors.affiliation: Neurosurgical Department of The Second Affiliated Hospital, Soochow University, Suzhou 215004, P.R. China.
authors.forename: Zhao-Hui
authors.initials: ZH
authors.lastname: Lu
authors.affiliation: Neurosurgical Department of Shanghai Tenth People's Hospital, Tongji University, Shanghai 200072, P.R. China.
authors.forename: Ke
authors.initials: K
authors.lastname: Lv
authors.affiliation: Neurosurgical Department of The Second Affiliated Hospital, Soochow University, Suzhou 215004, P.R. China.
authors.forename: Jin-Shi
authors.initials: JS
authors.lastname: Zhang
authors.affiliation: Neurosurgical Department of Suzhou Seventh People's Hospital, Suzhou 215004, P.R. China.
authors.forename: Chun-Gang
authors.initials: CG
authors.lastname: Dai
authors.affiliation: Neurosurgical Department of Suzhou Seventh People's Hospital, Suzhou 215004, P.R. China.
authors.forename: Bin
authors.initials: B
authors.lastname: Liu
authors.affiliation: Neurosurgical Department of Suzhou Seventh People's Hospital, Suzhou 215004, P.R. China.
authors.forename: Xiao-Yu
authors.initials: XY
authors.lastname: Ma
authors.affiliation: Neurosurgical Department of Suzhou Seventh People's Hospital, Suzhou 215004, P.R. China.
authors.forename: Lin-Ming
authors.initials: LM
authors.lastname: He
authors.affiliation: Neurosurgical Department of Suzhou Seventh People's Hospital, Suzhou 215004, P.R. China.
authors.forename: Jing-Yun
authors.initials: JY
authors.lastname: Jia
authors.affiliation: Neurosurgical Department of The Second Affiliated Hospital, Soochow University, Suzhou 215004, P.R. China.
authors.forename: Yan-Ming
authors.initials: YM
authors.lastname: Chen
authors.affiliation: Neurosurgical Department of The Second Affiliated Hospital, Soochow University, Suzhou 215004, P.R. China.
authors.forename: Xing-Liang
authors.initials: XL
authors.lastname: Dai
authors.affiliation: Neurosurgical Department of The Second Affiliated Hospital, Soochow University, Suzhou 215004, P.R. China.
authors.forename: Ai-Dong
authors.initials: AD
authors.lastname: Wang
authors.affiliation: Neurosurgical Department of The Second Affiliated Hospital, Soochow University, Suzhou 215004, P.R. China.
authors.forename: Jun
authors.initials: J
authors.lastname: Dong
authors.affiliation: Neurosurgical Department of Shanghai Tenth People's Hospital, Tongji University, Shanghai 200072, P.R. China.
authors.forename: Quan-Bin
authors.initials: QB
authors.lastname: Zhang
authors.affiliation: Neurosurgical Department of The Second Affiliated Hospital, Soochow University, Suzhou 215004, P.R. China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Lan
authors.affiliation: Neurosurgical Department of The Second Affiliated Hospital, Soochow University, Suzhou 215004, P.R. China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Huang
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis; D015214:Antigens, Differentiation, Myelomonocytic / Q000096:biosynthesis; D001932:Brain Neoplasms / Q000235:genetics / Q000473:pathology*; D039481:CD11b Antigen / Q000096:biosynthesis; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D005910:Glioma / Q000235:genetics / Q000473:pathology*; D049452:Green Fluorescent Proteins / Q000235:genetics*; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000096:biosynthesis; D019394:Ki-67 Antigen / Q000096:biosynthesis; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D008822:Mice, Transgenic; D009336:Necrosis / Q000235:genetics / Q000473:pathology*; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic; D014183:Transplantation, Heterologous; D059016:Tumor Microenvironment / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D039481:CD11b Antigen; D049452:Green Fluorescent Proteins; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D019394:Ki-67 Antigen; D014409:Tumor Necrosis Factor-alpha; C081026:CD68 protein, mouse; D000097382:CD68 Molecule; C497443:Hif1a protein, mouse; C498355:Mki67 protein, mouse