title: Glioma initiating cells contribute to malignant transformation of host glial cells during tumor tissue remodeling via PDGF signaling.
abstract: BACKGROUND
  Glioma initiating cells (GICs) play important roles in tumor initiation and progression. However, interactions between tumor cells and host cells of local tumor microenvironment are kept largely unknown. Besides GICs and their progeny cells, whether adjacent normal glial cells contribute to tumorigenesis during glioma tissue remodeling deserves further investigation.
  
  
  METHODS
  Red fluorescence protein (RFP) gene was stably transfected into human GIC cells lines SU3 and U87, then were transplanted intracerebrally into athymic nude mice with whole-body green fluorescence protein (GFP) expression. The interactions between GICs and host cells in vivo were observed during tissue remodeling processes initiated by hGICs. The biological characteristics of host glial cells with high proliferation capability cloned from the xenograft were further assayed.
  
  
  RESULTS
  In a SU3 initiated dual-fluorescence xenograft glioma model, part of host cells cloned from the intracerebral tumors were found acquiring the capability of unlimited proliferation. PCR and FISH results indicated that malignant transformed cells were derived from host cells; cell surface marker analysis showed these cells expressed murine oligodendrocyte specific marker CNP, and oligodendrocyte progenitor cells (OPCs) specific markers PDGFR-α and NG2. Chromosomal analysis showed these cells were super tetraploid. In vivo studies showed they behaved with high invasiveness activity and nearly 100% tumorigenic ratio. Compared with SU3 cells with higher PDGF-B expression, GICs derived from U87 cells with low level of PDGF-B expression failed to induce host cell transformation.
  
  
  CONCLUSIONS
  Primary high invasive GICs SU3 contribute to transformation of adjacent normal host glial cells in local tumor microenvironment possibly via PDGF/PDGFR signaling activation, which deserved further investigation.
authors.affiliation: Department of Neurosurgery and Brain Tumor Research Laboratory, The Second Affiliated Hospital of Soochow University, Suzhou, China.
authors.forename: Yanming
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Neurosurgery and Brain Tumor Research Laboratory, The Second Affiliated Hospital of Soochow University, Suzhou, China.
authors.forename: Zhongyong
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery and Brain Tumor Research Laboratory, The Second Affiliated Hospital of Soochow University, Suzhou, China.
authors.forename: Xingliang
authors.initials: X
authors.lastname: Dai
authors.affiliation: Department of Neurosurgery, Suzhou Kowloon Hospital of Shanghai Jiaotong University School of Medicine, 118 Wansheng Street, 215021, Suzhou, China.
authors.forename: Xifeng
authors.initials: X
authors.lastname: Fei
authors.affiliation: Department of Neurosurgery and Brain Tumor Research Laboratory, The Second Affiliated Hospital of Soochow University, Suzhou, China.
authors.forename: Yuntian
authors.initials: Y
authors.lastname: Shen
authors.affiliation: Department of Neurosurgery and Brain Tumor Research Laboratory, The Second Affiliated Hospital of Soochow University, Suzhou, China.
authors.forename: Mingxia
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Department of Neurosurgery and Brain Tumor Research Laboratory, The Second Affiliated Hospital of Soochow University, Suzhou, China.
authors.forename: Aidong
authors.initials: A
authors.lastname: Wang
authors.affiliation: Laboratory of Molecular Neuro-oncology, Texas Children's Cancer Center, Baylor College of Medicine, Houston, TX, USA.
authors.forename: Xiaonan
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Neurosurgery, Suzhou Kowloon Hospital of Shanghai Jiaotong University School of Medicine, 118 Wansheng Street, 215021, Suzhou, China.
authors.forename: Zhimin
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery and Brain Tumor Research Laboratory, The Second Affiliated Hospital of Soochow University, Suzhou, China. Electronic address: hq1936@163.com.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Huang
authors.affiliation: Department of Neurosurgery and Brain Tumor Research Laboratory, The Second Affiliated Hospital of Soochow University, Suzhou, China. Electronic address: djdongjun@163.com.
authors.forename: Jun
authors.initials: J
authors.lastname: Dong
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic; D004195:Disease Models, Animal; D005910:Glioma / Q000473:pathology*; D049452:Green Fluorescent Proteins / Q000235:genetics; D006801:Humans; D008164:Luminescent Proteins / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D014411:Neoplastic Stem Cells / Q000473:pathology*; D009457:Neuroglia / Q000166:cytology; D010982:Platelet-Derived Growth Factor / Q000378:metabolism*; D020574:Proto-Oncogene Proteins c-sis / Q000096:biosynthesis / Q000378:metabolism; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000096:biosynthesis / Q000378:metabolism*; D015398:Signal Transduction; D014183:Transplantation, Heterologous; D059016:Tumor Microenvironment; D000097573:Red Fluorescent Protein
chemical_list: D049452:Green Fluorescent Proteins; D008164:Luminescent Proteins; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D020796:Receptor, Platelet-Derived Growth Factor alpha; D000097573:Red Fluorescent Protein; C075278:platelet-derived growth factor A
keywords: Dual-fluorescence tumor model; Glioma initiating cells; Malignant transformation; Tumor microenvironment