PMID- 22786655
OWN - NLM
STAT- MEDLINE
DCOM- 20130107
LR  - 20220310
IS  - 1096-9896 (Electronic)
IS  - 0022-3417 (Linking)
VI  - 228
IP  - 3
DP  - 2012 Nov
TI  - Transcriptional profiling of human glioblastoma vessels indicates a key role of 
      VEGF-A and TGFbeta2 in vascular abnormalization.
PG  - 378-90
LID - 10.1002/path.4072 [doi]
AB  - Glioblastoma are aggressive astrocytic brain tumours characterized by 
      microvascular proliferation and an abnormal vasculature, giving rise to brain 
      oedema and increased patient morbidity. Here, we have characterized the 
      transcriptome of tumour-associated blood vessels and describe a gene signature 
      clearly associated with pleomorphic, pathologically altered vessels in human 
      glioblastoma (grade IV glioma). We identified 95 genes differentially expressed 
      in glioblastoma vessels, while no significant differences in gene expression were 
      detected between vessels in non-malignant brain and grade II glioma. Differential 
      vascular expression of ANGPT2, CD93, ESM1, ELTD1, FILIP1L and TENC1 in human 
      glioblastoma was validated by immunohistochemistry, using a tissue microarray. 
      Through qPCR analysis of gene induction in primary endothelial cells, we provide 
      evidence that increased VEGF-A and TGFbeta2 signalling in the tumour 
      microenvironment is sufficient to invoke many of the changes in gene expression 
      noted in glioblastoma vessels. Notably, we found an enrichment of Smad target 
      genes within the distinct gene signature of glioblastoma vessels and a 
      significant increase of Smad signalling complexes in the vasculature of human 
      glioblastoma in situ. This indicates a key role of TGFbeta signalling in regulating 
      vascular phenotype and suggests that, in addition to VEGF-A, TGFbeta2 may represent 
      a new target for vascular normalization therapy.
CI  - Copyright (c) 2012 Pathological Society of Great Britain and Ireland. Published by 
      John Wiley & Sons, Ltd.
FAU - Dieterich, Lothar C
AU  - Dieterich LC
AD  - Department of Immunology, Genetics and Pathology, Rudbeck Laboratory, Uppsala 
      University, Sweden.
FAU - Mellberg, Sofie
AU  - Mellberg S
FAU - Langenkamp, Elise
AU  - Langenkamp E
FAU - Zhang, Lei
AU  - Zhang L
FAU - Zieba, Agata
AU  - Zieba A
FAU - Salomaki, Henriikka
AU  - Salomaki H
FAU - Teichert, Martin
AU  - Teichert M
FAU - Huang, Hua
AU  - Huang H
FAU - Edqvist, Per-Henrik
AU  - Edqvist PH
FAU - Kraus, Theo
AU  - Kraus T
FAU - Augustin, Hellmut G
AU  - Augustin HG
FAU - Olofsson, Tommie
AU  - Olofsson T
FAU - Larsson, Erik
AU  - Larsson E
FAU - Soderberg, Ola
AU  - Soderberg O
FAU - Molema, Grietje
AU  - Molema G
FAU - Ponten, Fredrik
AU  - Ponten F
FAU - Georgii-Hemming, Patrik
AU  - Georgii-Hemming P
FAU - Alafuzoff, Irina
AU  - Alafuzoff I
FAU - Dimberg, Anna
AU  - Dimberg A
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120831
PL  - England
TA  - J Pathol
JT  - The Journal of pathology
JID - 0204634
RN  - 0 (Transforming Growth Factor beta2)
RN  - 0 (Vascular Endothelial Growth Factor A)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Blood Vessels/*physiopathology
MH  - Brain Neoplasms/blood supply/pathology/*physiopathology
MH  - Case-Control Studies
MH  - Endothelium, Vascular/pathology/physiopathology
MH  - *Gene Expression Profiling
MH  - Gene Expression Regulation, Neoplastic/physiology
MH  - Glioblastoma/blood supply/pathology/*physiopathology
MH  - Humans
MH  - Laser Capture Microdissection
MH  - Microarray Analysis
MH  - Middle Aged
MH  - Neoplasm Grading
MH  - Pericytes/pathology/physiology
MH  - Signal Transduction/physiology
MH  - Transforming Growth Factor beta2/genetics/*physiology
MH  - Vascular Endothelial Growth Factor A/genetics/*physiology
EDAT- 2012/07/13 06:00
MHDA- 2013/01/08 06:00
CRDT- 2012/07/13 06:00
PHST- 2011/06/11 00:00 [received]
PHST- 2012/07/03 00:00 [revised]
PHST- 2012/07/04 00:00 [accepted]
PHST- 2012/07/13 06:00 [entrez]
PHST- 2012/07/13 06:00 [pubmed]
PHST- 2013/01/08 06:00 [medline]
AID - 10.1002/path.4072 [doi]
PST - ppublish
SO  - J Pathol. 2012 Nov;228(3):378-90. doi: 10.1002/path.4072. Epub 2012 Aug 31.