PMID- 20697979
OWN - NLM
STAT- MEDLINE
DCOM- 20110428
LR  - 20211020
IS  - 2629-3277 (Electronic)
IS  - 2629-3277 (Linking)
VI  - 7
IP  - 1
DP  - 2011 Mar
TI  - Glioma stem/progenitor cells contribute to neovascularization via 
      transdifferentiation.
PG  - 141-52
LID - 10.1007/s12015-010-9169-7 [doi]
AB  - OBJECTIVE: Previous studies suggest that tumor cells might be the progenitor for 
      tumor vasculature. Whether vascular tube formation from transdifferentiation of 
      human glioma stem/progenitor cells (hGSPCs) contribute to angiogenesis of gliomas 
      remain largely uncertain. METHODS: hGSPCs were isolated from thirteen surgical 
      specimens of gliomas and cultured in medium favored for stem cell growth. In 
      vitro transdifferentiation of hGSPCs was performed under hypoxia. Expression of 
      vascular endothelial cells (VECs) markers CD31, CD34, kinase insert domain 
      receptor (KDR), and von Willebrand factor (vWF) were analyzed with real-time 
      quantitative RT-PCR and immunofluorescence techniques. Vasculogenic mimicry of 
      hGSPCs was evaluated in a tumor stem cell xenograft model in vivo. Relationships 
      between content of hGSPCs and expression levels of both VECs markers and 
      proangiogenic factors in large number of clinical specimens were further 
      investigated in glioma tissue microarray. RESULTS: In vitro, hGSPCs can 
      transdifferentiate into VECs under hypoxia, they manifested typical "flagstone" 
      pattern when cultivated in medium containing VEGF for a few days; when cultivated 
      on Matrigel they were capable of forming capillary-like structures. Expression of 
      VECs markers including CD31, CD34, KDR, and vWF were significantly up-regulated 
      after transdifferentiation. Human leukocyte antigen (HLA) positively stained 
      vessels were observed inside the xenograft tumors after intracerebral 
      transplantation of hGSPCs in athymic nude mice, implied part of tumor cells with 
      human origin were involved in formation of tumor vessels. In surgical specimens 
      of human glioma, tumor vascular cells coexpressing the markers of early VECs 
      (CD34) and markers of hGSPCs (ABCG2 and nestin) suggest that these vascular cells 
      may stemmed from hGSPCs. CONCLUSIONS: Our observations suggest the functional 
      role of hGSPCs as endothelial progenitors, which have properties that give rise 
      to VECs, and have the ability to form vascular endothelial tubes. However, 
      unspecific markers (ABCG2, nestin) that stain for both endothelial as well as 
      glioma stem cells, were found to be expressed in tumor vasculature of human 
      specimen, and limit further interpretation of this finding.
FAU - Dong, Jun
AU  - Dong J
AD  - Department of Neurosurgery, The 2nd Affiliated Hospital of Suzhou University, 
      1055 Sanxiang Road, Suzhou 215004, People's Republic of China.
FAU - Zhao, Yaodong
AU  - Zhao Y
FAU - Huang, Qiang
AU  - Huang Q
FAU - Fei, Xifeng
AU  - Fei X
FAU - Diao, Yi
AU  - Diao Y
FAU - Shen, Yuntian
AU  - Shen Y
FAU - Xiao, Hong
AU  - Xiao H
FAU - Zhang, Tianyi
AU  - Zhang T
FAU - Lan, Qing
AU  - Lan Q
FAU - Gu, Xiaosong
AU  - Gu X
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Stem Cell Rev Rep
JT  - Stem cell reviews and reports
JID - 101752767
RN  - 0 (Angiogenesis Inducing Agents)
RN  - 0 (Biomarkers)
SB  - IM
MH  - Angiogenesis Inducing Agents/metabolism
MH  - Animals
MH  - Biomarkers/metabolism
MH  - Cell Hypoxia/genetics
MH  - Cell Proliferation
MH  - Cell Shape
MH  - *Cell Transdifferentiation
MH  - Endothelial Cells/metabolism/pathology
MH  - Fluorescent Antibody Technique
MH  - Gene Expression Regulation, Neoplastic
MH  - Glioma/*blood supply/genetics/*pathology
MH  - Humans
MH  - Mice
MH  - Mice, Nude
MH  - Neoplastic Stem Cells/*pathology
MH  - Neovascularization, Pathologic/genetics/*pathology
MH  - Side-Population Cells/pathology
MH  - Transcription, Genetic
MH  - Xenograft Model Antitumor Assays
EDAT- 2010/08/11 06:00
MHDA- 2011/04/29 06:00
CRDT- 2010/08/11 06:00
PHST- 2010/08/11 06:00 [entrez]
PHST- 2010/08/11 06:00 [pubmed]
PHST- 2011/04/29 06:00 [medline]
AID - 10.1007/s12015-010-9169-7 [doi]
PST - ppublish
SO  - Stem Cell Rev Rep. 2011 Mar;7(1):141-52. doi: 10.1007/s12015-010-9169-7.