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Transcriptional pro...
Transcriptional profiling of human glioblastoma vessels indicates a key role of VEGF-A and TGFβ2 in vascular abnormalization
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- Dieterich, Lothar C. (author)
- Uppsala universitet,Institutionen för immunologi, genetik och patologi
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- Mellberg, Sofie (author)
- Uppsala universitet,Cancer och vaskulärbiologi,Dimberg
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- Langenkamp, Elise (author)
- Uppsala universitet,Cancer och vaskulärbiologi,Dimberg
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- Zhang, Lei (author)
- Uppsala universitet,Cancer och vaskulärbiologi,Dimberg
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- Zieba, Agata (author)
- Uppsala universitet,Molekylär och morfologisk patologi,Pontén
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- Salomäki, Henriikka (author)
- Uppsala universitet,Institutionen för immunologi, genetik och patologi
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Teichert, M. (author)
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- Huang, Hua (author)
- Uppsala universitet,Cancer och vaskulärbiologi,Dimberg
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- Edqvist, Per-Henrik (author)
- Uppsala universitet,Molekylär och morfologisk patologi,Pontén
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Kraus, T. (author)
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Augustin, H. G. (author)
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- Olofsson, Tommie (author)
- Uppsala universitet,Institutionen för immunologi, genetik och patologi
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- Larsson, Erik (author)
- Uppsala universitet,Molekylär och morfologisk patologi,Alafuzoff
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- Söderberg, Ola (author)
- Uppsala universitet,Molekylära verktyg,Söderberg
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Molema, G. (author)
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- Pontén, Fredrik (author)
- Uppsala universitet,Molekylär och morfologisk patologi,Pontén
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- Georgii-Hemming, Patrik (author)
- Uppsala universitet,Medicinsk genetik,Dahl
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- Alafuzoff, Irina (author)
- Uppsala universitet,Molekylär och morfologisk patologi,Alafuzoff
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- Dimberg, Anna (author)
- Uppsala universitet,Cancer och vaskulärbiologi,Dimberg
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(creator_code:org_t)
- 2012-08-31
- 2012
- English.
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In: Journal of Pathology. - : Wiley. - 0022-3417 .- 1096-9896. ; 228:3, s. 378-390
- Related links:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Subject headings
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- 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 TGFβ2 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 TGFβ signalling in regulating vascular phenotype and suggests that, in addition to VEGF-A, TGFβ2 may represent a new target for vascular normalization therapy.
Keyword
- angiogenesis
- brain tumour
- growth factor
- laser microdissection
- microarray
- tumour endothelial marker
- vasculature
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Dieterich, Lotha ...
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Mellberg, Sofie
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Langenkamp, Elis ...
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Zhang, Lei
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Zieba, Agata
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Salomäki, Henrii ...
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show more...
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Teichert, M.
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Huang, Hua
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Edqvist, Per-Hen ...
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Kraus, T.
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Augustin, H. G.
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Olofsson, Tommie
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Larsson, Erik
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Söderberg, Ola
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Molema, G.
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Pontén, Fredrik
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Georgii-Hemming, ...
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Alafuzoff, Irina
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Dimberg, Anna
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show less...
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Journal of Patho ...
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Uppsala University