PMID- 16354539
OWN - NLM
STAT- MEDLINE
DCOM- 20060329
LR  - 20061115
IS  - 0161-6412 (Print)
IS  - 0161-6412 (Linking)
VI  - 27
IP  - 8
DP  - 2005 Dec
TI  - Differential expression of angiopoietin-1 and angiopoietin-2 may enhance 
      recruitment of bone-marrow-derived endothelial precursor cells into brain tumors.
PG  - 801-6
AB  - OBJECTIVES: Angiogenesis is necessary for sustained neoplastic development. The 
      angiopoietins Ang-1 and Ang-2 have been implicated in the regulation of this 
      process; recent reports have suggested that a net gain in Ang-2 activity may be 
      an initiating factor for tumor angiogenesis. We examined the recruitment of bone 
      marrow-derived endothelial precursor cells into developing tumor neovasculature, 
      and the spatial relationship between these cells and angiopoietin (Ang-1 and 
      Ang-2) expression. METHODS: For this study T-cell depleted knockout mice 
      (RAG-2/KO-5.2) were lethally irradiated and their bone marrow was reconstituted 
      by bone marrow cells (BMCs) from transgenic mice (C57BL/Ka-Thy1.1) expressing 
      green fluorescent protein (GFP). Rat glioma cells (RT-2/RAG) were then injected 
      into the transplanted animals to form solid brain tumors. The animals were killed 
      and their brains were analysed using immunohistochemistry and 
      fluorescence-activated cell sorting. RESULTS: We found that BMCs migrated 
      preferentially into the tumor when compared to adjacent healthy brain parenchyma. 
      Furthermore, GFP+/CD34+ cells represented up to 8% of endothelial-like cells 
      within the walls of tumor blood vessels. In the tumor, significant colocalization 
      of Ang-2 with GFP+/CD34+ cells was noted (>80%), but colocalization with Ang-1 
      never exceeded 20%. In normal tissue directly surrounding the tumor, GFP+/CD34+ 
      cells colocalized strongly with both angiopoietins (>75% and >70% for Ang-1 and 
      Ang-2, respectively). DISCUSSION: The relative increase in angiopoietin-2 
      activity in brain tumors may result in the creation of a pro-angiogenic 
      environment that enhances the recruitment of putative bone marrow-derived 
      endothelial precursor cells into the tumor's developing vascular tree.
FAU - Udani, V
AU  - Udani V
AD  - Department of Neurosurgery, Stanford University Medical Center, California, USA. 
      vikudani@stanford.edu
FAU - Santarelli, J
AU  - Santarelli J
FAU - Yung, Y
AU  - Yung Y
FAU - Cheshier, S
AU  - Cheshier S
FAU - Andrews, A
AU  - Andrews A
FAU - Kasad, Z
AU  - Kasad Z
FAU - Tse, V
AU  - Tse V
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Neurol Res
JT  - Neurological research
JID - 7905298
RN  - 0 (Angiopoietin-1)
RN  - 0 (Angiopoietin-2)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Neoplasm Proteins)
RN  - 0 (Rag2 protein, mouse)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - 147336-22-9 (Green Fluorescent Proteins)
SB  - IM
MH  - Angiopoietin-1/biosynthesis/genetics/*physiology
MH  - Angiopoietin-2/biosynthesis/genetics/*physiology
MH  - Animals
MH  - Bone Marrow Cells/*physiology
MH  - Brain Neoplasms/*blood supply
MH  - Cell Line, Tumor/transplantation
MH  - Cell Lineage
MH  - Cell Movement/physiology
MH  - DNA-Binding Proteins/deficiency
MH  - Endothelial Cells/cytology
MH  - Endothelium, Vascular/*cytology
MH  - *Gene Expression Regulation, Neoplastic
MH  - Genes, Reporter
MH  - Glioma/*blood supply
MH  - Green Fluorescent Proteins/analysis/genetics
MH  - Hematopoietic Stem Cells/*physiology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Mice, Nude
MH  - Mice, SCID
MH  - Mice, Transgenic
MH  - Neoplasm Proteins/biosynthesis/genetics/*physiology
MH  - Neoplasm Transplantation
MH  - Neovascularization, Pathologic/*physiopathology
MH  - Radiation Chimera
MH  - Rats
MH  - Transplantation, Heterologous
MH  - Vascular Endothelial Growth Factor A/analysis
EDAT- 2005/12/16 09:00
MHDA- 2006/03/30 09:00
CRDT- 2005/12/16 09:00
PHST- 2005/12/16 09:00 [pubmed]
PHST- 2006/03/30 09:00 [medline]
PHST- 2005/12/16 09:00 [entrez]
AID - 10.1179/016164105X49319 [doi]
PST - ppublish
SO  - Neurol Res. 2005 Dec;27(8):801-6. doi: 10.1179/016164105X49319.