title: [Glioma stem cells enhanced angiogenesis and its relationship with microvessel].
abstract: OBJECTIVE
  To dynamically observe how glioma stem cells promote the tumor formation and angiogenesis, and to study the correlation between the distribution of glioma stem cells and microvessels within different growth stages of subcutaneous tumor.
  
  
  METHODS
  Stem cell medium culture and magnetic activated cell sorting were carried out to obtain CD133+ cells from C6 rat glioma cell line. Sprague Dawley (SD) rat ears model were established to observe glioma stem cells promoting blood vessel formation. Subcutaneous glioma model of C6 and immunohistochemical staining of hypoxia inducible factor-1α (HIF-1α) and CD133 were used to investigate the relationship between distribution of glioma stem cells and microvessels. Expressions of CD133 protein in each stage of the subcutaneous tumor were detected by Western blot.
  
  
  RESULTS
  Isolation and identification of glioma stem cells deprived from C6 glioma cell line successfully, the establishment of ears model showed real-time dynamic observation of CD133+ cells involved in angiogenesis and tumor formation. SD rat model of subcutaneous glioma showed the initial of tumor formation, CD133+ cells scattered. With tumor growth, CD133+ cells began to tend to capillaries, in late distributed clusters in perivascular. Meanwhile as tumor growth, CD133 protein expression was gradually increased: the values of Western blot analysis of CD133 expression on 6, 9, 12, 15, 20 d were 0.208±0.004, 0.282±0.003, 0.360±0.004, 0.564±0.135, 0.756±0.007, the differences were significant between different groups (F=2601.681, P<0.01). At a high magnification, the CD133 scores with immunohistochemical staining on 6, 9, 12, 15 d were 0.8±0.4, 2.4±0.5, 4.0 ± 0.7, 6.0±0.7; HIF-1α scores were 0.8±0.4, 2.8±0.8, 5.0±0.7, 6.8±0.4. By Spearman rank correlation analysis found that the relationship between CD133 and HIF-1α expression was positively correlated (r=0.921, P<0.01).
  
  
  CONCLUSIONS
  Glioma stem cells promote angiogenesis more than non-stem cells; HIF-1α and its downstream gene product might mediate the distribution of glioma stem cells around the perivascular.
authors.affiliation: Department of Neurosurgery, Tianjin Medical University General Hospital & Laboratory of Neuro-oncology, Tianjin Neurological Institute, Tianjin 300052, China.
authors.forename: Sheng-ping
authors.initials: SP
authors.lastname: Yu
authors.forename: Xue-jun
authors.initials: XJ
authors.lastname: Yang
authors.forename: Bin
authors.initials: B
authors.lastname: Zhang
authors.forename: Hao-lang
authors.initials: HL
authors.lastname: Ming
authors.forename: Bin
authors.initials: B
authors.lastname: Liu
authors.forename: Zhi-feng
authors.initials: ZF
authors.lastname: Liu
authors.forename: Bing-cheng
authors.initials: BC
authors.lastname: Ren
authors.forename: Cong
authors.initials: C
authors.lastname: Chen
authors.forename: Wei
authors.initials: W
authors.lastname: Gao
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D005910:Glioma / Q000098:blood supply / Q000378:metabolism / Q000473:pathology*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D055806:Microvessels / Q000473:pathology; D009368:Neoplasm Transplantation; D014411:Neoplastic Stem Cells / Q000473:pathology*; D009389:Neovascularization, Pathologic / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: C497444:Hif1a protein, rat; D051795:Hypoxia-Inducible Factor 1, alpha Subunit