title: Malignant transformation of host stromal ﬁbroblasts derived from the bone marrow traced in a dual-color fluorescence xenograft tumor model.
abstract: Solid tumors are abnormal tissues containing tumor and non-tumor cells, also known as tumor stromal cells. However, the malignant potential of tumor stromal cells remains largely unknown. The aim of the present study was to investigate the malignant potential of host bone marrow‑derived stroma cells in transplanted subcutaneous tumors of the glioma stem/progenitor cells (GSPCs) labeled using the dual-color fluorescent tracer technique. The previously established human glioma stem/progenitor cell line SU3 was transfected with red fluorescence protein (SU3-RFP) and transplanted subcutaneously into green fluorescent protein (GFP) transgenic nude mice and chimeric mice in which GFP was only expressed by bone marrow-derived cells (BMDCs). The xenograft tumors were subcultured in vitro and two immortalized GFP-expressing stromal cell lines were cloned from the transplanted tumors. The two cloned cell lines showed an accelerated growth rate, loss of cell contact inhibition, high cloning efficiency, and high DNA content and telocentric (murine) chromosomes with heteroploid characteristics. The tumorigenesis rate (10/10, 1x10(6)) of these host stromal cells was further evidence of malignant transformation. Immunofluorescence assay of the two host cell lines showed that they expressed fibroblast markers such as FAP, S100A4 and α-SMA, as well as mesenchymal cell markers such as CD44 and CD105. In conclusion, bone marrow-derived stromal ﬁbroblasts recruited to tumors have the potential for malignant transformation induced by the tumor microenvironment, which provides new evidence for the role of the stroma in malignant transformation.
authors.affiliation: Department of Neurosurgery, the Second Affiliated Hospital of Soochow University, Jinchang, Suzhou 215004, P.R. China.
authors.forename: Xingliang
authors.initials: X
authors.lastname: Dai
authors.affiliation: Department of Neurosurgery, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China.
authors.forename: Hua
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of Neurosurgery, the Second Affiliated Hospital of Soochow University, Jinchang, Suzhou 215004, P.R. China.
authors.forename: Yanming
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Neurosurgery, the Second Affiliated Hospital of Soochow University, Jinchang, Suzhou 215004, P.R. China.
authors.forename: Jinding
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of Neurosurgery, the Second Affiliated Hospital of Soochow University, Jinchang, Suzhou 215004, P.R. China.
authors.forename: Haiyang
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China.
authors.forename: Jia
authors.initials: J
authors.lastname: Shi
authors.affiliation: Department of Neurosurgery, Suzhou Kowloon Hospital, Shanghai Jiaotong University School of Medicine, Jinchang, Suzhou, 215021, P.R. China.
authors.forename: Xifeng
authors.initials: X
authors.lastname: Fei
authors.affiliation: Department of Neurosurgery, Suzhou Kowloon Hospital, Shanghai Jiaotong University School of Medicine, Jinchang, Suzhou, 215021, P.R. China.
authors.forename: Zhimin
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery, the Second Affiliated Hospital of Soochow University, Jinchang, Suzhou 215004, P.R. China.
authors.forename: Aidong
authors.initials: A
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery, the Second Affiliated Hospital of Soochow University, Jinchang, Suzhou 215004, P.R. China.
authors.forename: Jun
authors.initials: J
authors.lastname: Dong
authors.affiliation: Department of Neurosurgery, the Second Affiliated Hospital of Soochow University, Jinchang, Suzhou 215004, P.R. China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Lan
authors.affiliation: Department of Neurosurgery, the Second Affiliated Hospital of Soochow University, Jinchang, Suzhou 215004, P.R. China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Huang
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000473:pathology; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D004195:Disease Models, Animal; D005347:Fibroblasts / Q000473:pathology*; D049452:Green Fluorescent Proteins / Q000235:genetics; D006801:Humans; D051379:Mice; D017154:Stromal Cells / Q000473:pathology*; D059016:Tumor Microenvironment / Q000235:genetics*; D023041:Xenograft Model Antitumor Assays
chemical_list: D049452:Green Fluorescent Proteins