Publication

Transcriptional profiling of human glioblastoma vessels indicates a key role of VEGF-A and TGF beta 2 in vascular abnormalization

Dieterich, L. C., Mellberg, S., Langenkamp, E., Zhang, L., Zieba, A., Salomaki, H., Teichert, M., Huang, H., Edqvist, P-H., Kraus, T., Augustin, H. G., Olofsson, T., Larsson, E., Soderberg, O., Molema, G., Ponten, F., Georgii-Hemming, P., Alafuzoff, I. & Dimberg, A. Nov-2012 In : JOURNAL OF PATHOLOGY. 228, 3, p. 378-390 13 p.

Research output: Scientific - peer-reviewArticle

APA

Dieterich, L. C., Mellberg, S., Langenkamp, E., Zhang, L., Zieba, A., Salomaki, H., ... Dimberg, A. (2012). Transcriptional profiling of human glioblastoma vessels indicates a key role of VEGF-A and TGF beta 2 in vascular abnormalization. JOURNAL OF PATHOLOGY, 228(3), 378-390. DOI: 10.1002/path.4072

Author

Dieterich, Lothar C.; Mellberg, Sofie; Langenkamp, Elise; Zhang, Lei; Zieba, Agata; Salomaki, Henriikka; Teichert, Martin; Huang, Hua; Edqvist, Per-Henrik; Kraus, Theo; Augustin, Hellmut G.; Olofsson, Tommie; Larsson, Erik; Soderberg, Ola; Molema, Grietje; Ponten, Fredrik; Georgii-Hemming, Patrik; Alafuzoff, Irina; Dimberg, Anna / Transcriptional profiling of human glioblastoma vessels indicates a key role of VEGF-A and TGF beta 2 in vascular abnormalization.

In: JOURNAL OF PATHOLOGY, Vol. 228, No. 3, 11.2012, p. 378-390.

Research output: Scientific - peer-reviewArticle

Harvard

Dieterich, LC, Mellberg, S, Langenkamp, E, Zhang, L, Zieba, A, Salomaki, H, Teichert, M, Huang, H, Edqvist, P-H, Kraus, T, Augustin, HG, Olofsson, T, Larsson, E, Soderberg, O, Molema, G, Ponten, F, Georgii-Hemming, P, Alafuzoff, I & Dimberg, A 2012, 'Transcriptional profiling of human glioblastoma vessels indicates a key role of VEGF-A and TGF beta 2 in vascular abnormalization' JOURNAL OF PATHOLOGY, vol 228, no. 3, pp. 378-390. DOI: 10.1002/path.4072

Standard

Transcriptional profiling of human glioblastoma vessels indicates a key role of VEGF-A and TGF beta 2 in vascular abnormalization. / Dieterich, Lothar C.; Mellberg, Sofie; Langenkamp, Elise; Zhang, Lei; Zieba, Agata; Salomaki, Henriikka; Teichert, Martin; Huang, Hua; Edqvist, Per-Henrik; Kraus, Theo; Augustin, Hellmut G.; Olofsson, Tommie; Larsson, Erik; Soderberg, Ola; Molema, Grietje; Ponten, Fredrik; Georgii-Hemming, Patrik; Alafuzoff, Irina; Dimberg, Anna.

In: JOURNAL OF PATHOLOGY, Vol. 228, No. 3, 11.2012, p. 378-390.

Research output: Scientific - peer-reviewArticle

Vancouver

Dieterich LC, Mellberg S, Langenkamp E, Zhang L, Zieba A, Salomaki H et al. Transcriptional profiling of human glioblastoma vessels indicates a key role of VEGF-A and TGF beta 2 in vascular abnormalization. JOURNAL OF PATHOLOGY. 2012 Nov;228(3):378-390. Available from, DOI: 10.1002/path.4072


BibTeX

@article{403dc295f53f4588a2b03cccb4919014,
title = "Transcriptional profiling of human glioblastoma vessels indicates a key role of VEGF-A and TGF beta 2 in vascular abnormalization",
abstract = "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 TGF beta 2 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 TGF beta signalling in regulating vascular phenotype and suggests that, in addition to VEGF-A, TGF beta 2 may represent a new target for vascular normalization therapy. Copyright (c) 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.",
keywords = "brain tumour, vasculature, laser microdissection, microarray, growth factor, angiogenesis, tumour endothelial marker, ENDOTHELIAL GROWTH-FACTOR, TO-MESENCHYMAL TRANSITION, RECEPTOR TYROSINE KINASES, HUMAN PROTEIN ATLAS, STEM-LIKE CELLS, BRAIN-TUMORS, ASTROCYTIC TUMORS, MALIGNANT GLIOMAS, FACTOR-BETA, TGF-BETA",
author = "Dieterich, {Lothar C.} and Sofie Mellberg and Elise Langenkamp and Lei Zhang and Agata Zieba and Henriikka Salomaki and Martin Teichert and Hua Huang and Per-Henrik Edqvist and Theo Kraus and Augustin, {Hellmut G.} and Tommie Olofsson and Erik Larsson and Ola Soderberg and Grietje Molema and Fredrik Ponten and Patrik Georgii-Hemming and Irina Alafuzoff and Anna Dimberg",
year = "2012",
month = "11",
doi = "10.1002/path.4072",
volume = "228",
pages = "378--390",
journal = "JOURNAL OF PATHOLOGY",
issn = "0022-3417",
publisher = "Wiley-Blackwell",
number = "3",

}

RIS

TY - JOUR

T1 - Transcriptional profiling of human glioblastoma vessels indicates a key role of VEGF-A and TGF beta 2 in vascular abnormalization

AU - Dieterich,Lothar C.

AU - Mellberg,Sofie

AU - Langenkamp,Elise

AU - Zhang,Lei

AU - Zieba,Agata

AU - Salomaki,Henriikka

AU - Teichert,Martin

AU - Huang,Hua

AU - Edqvist,Per-Henrik

AU - Kraus,Theo

AU - Augustin,Hellmut G.

AU - Olofsson,Tommie

AU - Larsson,Erik

AU - Soderberg,Ola

AU - Molema,Grietje

AU - Ponten,Fredrik

AU - Georgii-Hemming,Patrik

AU - Alafuzoff,Irina

AU - Dimberg,Anna

PY - 2012/11

Y1 - 2012/11

N2 - 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 TGF beta 2 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 TGF beta signalling in regulating vascular phenotype and suggests that, in addition to VEGF-A, TGF beta 2 may represent a new target for vascular normalization therapy. Copyright (c) 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

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 TGF beta 2 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 TGF beta signalling in regulating vascular phenotype and suggests that, in addition to VEGF-A, TGF beta 2 may represent a new target for vascular normalization therapy. Copyright (c) 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

KW - brain tumour

KW - vasculature

KW - laser microdissection

KW - microarray

KW - growth factor

KW - angiogenesis

KW - tumour endothelial marker

KW - ENDOTHELIAL GROWTH-FACTOR

KW - TO-MESENCHYMAL TRANSITION

KW - RECEPTOR TYROSINE KINASES

KW - HUMAN PROTEIN ATLAS

KW - STEM-LIKE CELLS

KW - BRAIN-TUMORS

KW - ASTROCYTIC TUMORS

KW - MALIGNANT GLIOMAS

KW - FACTOR-BETA

KW - TGF-BETA

U2 - 10.1002/path.4072

DO - 10.1002/path.4072

M3 - Article

VL - 228

SP - 378

EP - 390

JO - JOURNAL OF PATHOLOGY

T2 - JOURNAL OF PATHOLOGY

JF - JOURNAL OF PATHOLOGY

SN - 0022-3417

IS - 3

ER -

ID: 5696350