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  • Dieterich, Lothar C.Uppsala universitet,Institutionen för immunologi, genetik och patologi (author)

Transcriptional profiling of human glioblastoma vessels indicates a key role of VEGF-A and TGFβ2 in vascular abnormalization

  • Article/chapterEnglish2012

Publisher, publication year, extent ...

  • 2012-08-31
  • Wiley,2012
  • printrdacarrier

Numbers

  • LIBRIS-ID:oai:DiVA.org:uu-184941
  • https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-184941URI
  • https://doi.org/10.1002/path.4072DOI

Supplementary language notes

  • Language:English
  • Summary in:English

Part of subdatabase

Classification

  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • De två första författarna delar förstaförfattarskapet.
  • 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.

Subject headings and genre

  • angiogenesis
  • brain tumour
  • growth factor
  • laser microdissection
  • microarray
  • tumour endothelial marker
  • vasculature

Added entries (persons, corporate bodies, meetings, titles ...)

  • Mellberg, SofieUppsala universitet,Cancer och vaskulärbiologi,Dimberg(Swepub:uu)somel030 (author)
  • Langenkamp, EliseUppsala universitet,Cancer och vaskulärbiologi,Dimberg(Swepub:uu)elila653 (author)
  • Zhang, LeiUppsala universitet,Cancer och vaskulärbiologi,Dimberg(Swepub:uu)leizh534 (author)
  • Zieba, AgataUppsala universitet,Molekylär och morfologisk patologi,Pontén(Swepub:uu)agazi628 (author)
  • Salomäki, HenriikkaUppsala universitet,Institutionen för immunologi, genetik och patologi (author)
  • Teichert, M. (author)
  • Huang, HuaUppsala universitet,Cancer och vaskulärbiologi,Dimberg(Swepub:uu)huahu114 (author)
  • Edqvist, Per-HenrikUppsala universitet,Molekylär och morfologisk patologi,Pontén(Swepub:uu)peedq227 (author)
  • Kraus, T. (author)
  • Augustin, H. G. (author)
  • Olofsson, TommieUppsala universitet,Institutionen för immunologi, genetik och patologi(Swepub:uu)tol26923 (author)
  • Larsson, ErikUppsala universitet,Molekylär och morfologisk patologi,Alafuzoff(Swepub:uu)eriklars (author)
  • Söderberg, OlaUppsala universitet,Molekylära verktyg,Söderberg(Swepub:uu)olasoder (author)
  • Molema, G. (author)
  • Pontén, FredrikUppsala universitet,Molekylär och morfologisk patologi,Pontén(Swepub:uu)fredpont (author)
  • Georgii-Hemming, PatrikUppsala universitet,Medicinsk genetik,Dahl(Swepub:uu)patrgeor (author)
  • Alafuzoff, IrinaUppsala universitet,Molekylär och morfologisk patologi,Alafuzoff(Swepub:uu)irial548 (author)
  • Dimberg, AnnaUppsala universitet,Cancer och vaskulärbiologi,Dimberg(Swepub:uu)annadimb (author)
  • Uppsala universitetInstitutionen för immunologi, genetik och patologi (creator_code:org_t)

Related titles

  • In:Journal of Pathology: Wiley228:3, s. 378-3900022-34171096-9896

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