Publication

The Angiogenic Makeup of Human Hepatocellular Carcinoma Does Not Favor Vascular Endothelial Growth Factor/Angiopoletin-Driven Sprouting Neovascularization

Zeng, W., Gouw, A. S. H., van den Heuvel, M. C., Zwiers, P. J., Zondervan, P. E., Poppema, S., Zhang, N., Platteel, I., de Jong, K. P. & Molema, G., Nov-2008, In : Hepatology. 48, 5, p. 1517-1527 11 p.

Research output: Contribution to journalArticleAcademicpeer-review

APA

Zeng, W., Gouw, A. S. H., van den Heuvel, M. C., Zwiers, P. J., Zondervan, P. E., Poppema, S., ... Molema, G. (2008). The Angiogenic Makeup of Human Hepatocellular Carcinoma Does Not Favor Vascular Endothelial Growth Factor/Angiopoletin-Driven Sprouting Neovascularization. Hepatology, 48(5), 1517-1527. https://doi.org/10.1002/hep.22490

Author

Zeng, Wenjiao ; Gouw, Annette S. H. ; van den Heuvel, Marius C. ; Zwiers, Peter J. ; Zondervan, Pieter E. ; Poppema, Sibrand ; Zhang, Nong ; Platteel, Inge ; de Jong, Koert P. ; Molema, Grietje. / The Angiogenic Makeup of Human Hepatocellular Carcinoma Does Not Favor Vascular Endothelial Growth Factor/Angiopoletin-Driven Sprouting Neovascularization. In: Hepatology. 2008 ; Vol. 48, No. 5. pp. 1517-1527.

Harvard

Zeng, W, Gouw, ASH, van den Heuvel, MC, Zwiers, PJ, Zondervan, PE, Poppema, S, Zhang, N, Platteel, I, de Jong, KP & Molema, G 2008, 'The Angiogenic Makeup of Human Hepatocellular Carcinoma Does Not Favor Vascular Endothelial Growth Factor/Angiopoletin-Driven Sprouting Neovascularization' Hepatology, vol. 48, no. 5, pp. 1517-1527. https://doi.org/10.1002/hep.22490

Standard

The Angiogenic Makeup of Human Hepatocellular Carcinoma Does Not Favor Vascular Endothelial Growth Factor/Angiopoletin-Driven Sprouting Neovascularization. / Zeng, Wenjiao; Gouw, Annette S. H.; van den Heuvel, Marius C.; Zwiers, Peter J.; Zondervan, Pieter E.; Poppema, Sibrand; Zhang, Nong; Platteel, Inge; de Jong, Koert P.; Molema, Grietje.

In: Hepatology, Vol. 48, No. 5, 11.2008, p. 1517-1527.

Research output: Contribution to journalArticleAcademicpeer-review

Vancouver

Zeng W, Gouw ASH, van den Heuvel MC, Zwiers PJ, Zondervan PE, Poppema S et al. The Angiogenic Makeup of Human Hepatocellular Carcinoma Does Not Favor Vascular Endothelial Growth Factor/Angiopoletin-Driven Sprouting Neovascularization. Hepatology. 2008 Nov;48(5):1517-1527. https://doi.org/10.1002/hep.22490


BibTeX

@article{f98ffd3751434cb48e33e6db54eab861,
title = "The Angiogenic Makeup of Human Hepatocellular Carcinoma Does Not Favor Vascular Endothelial Growth Factor/Angiopoletin-Driven Sprouting Neovascularization",
abstract = "Quantitative data on the expression of multiple factors that control angiogenesis in hepatocellular carcinoma (HCC) are limited. A better understanding of the mechanisms underlying angiogenesis in HCC will improve the rational choice of anti-angiogenic treatment. We quantified gene and protein expression of members of the vascular endothelial growth factor (VEGF) and angiopoietin systems and studied localization of VEGF, its receptors VEGFR-1 and VEGFR-2, Angiopoietin (Ang)-1 and Ang-2, and their receptor, in HCC in noncirrhotic and cirrhotic livers. We employed real-time reverse transcription polymerase chain reaction (RT-PCR), western blot, and immunohistology, and compared the outcome with highly angiogenic human renal cell carcinoma (RCC). HCC in noncirrhotic and cirrhotic livers expressed VEGF and its receptors to a similar extent as normal liver, although in cirrhotic background, VEGFR-2 levels in both tumor and adjacent tissue were decreased. Ang-1 expression was slightly increased compared with normal liver, whereas Tie-2 was strongly down-regulated in the tumor vasculature. Ang-2 messenger RNA (mRNA) levels were also low in HCCs of both noncirrhotic and cirrhotic livers, implying that VEGF-driven angiogenic sprouting accompanied by angiopoietin-driven vascular destabilization is not pronounced. In RCC, VEGF-A levels were one order of magnitude higher. At the same time, endothelially expressed Ang-2 was over 30-fold increased compared with expression in normal kidney, whereas Ang-1 expression was decreased. Conclusion: In hepatocellular carcinoma, tumor vascularization is not per se VEGF/angiopoietin driven. However, increased CD31 expression and morphological changes representative of sinusoidal capillarization in tumor vasculature indicate that vascular remodeling is taking place. This portends that therapeutic intervention of HCC at the level of the vasculature is optional, and that further studies into the molecular control thereof are warranted. (HEPATOLOGY 2008;48: 1517-1527.)",
keywords = "RENAL-CELL CARCINOMA, ANTIANGIOGENIC THERAPY, COLORECTAL-CANCER, LIVER METASTASES, GENE-EXPRESSION, FACTOR RECEPTOR, OVEREXPRESSION, ANGIOPOIETIN-2, APOPTOSIS, QUANTIFICATION",
author = "Wenjiao Zeng and Gouw, {Annette S. H.} and {van den Heuvel}, {Marius C.} and Zwiers, {Peter J.} and Zondervan, {Pieter E.} and Sibrand Poppema and Nong Zhang and Inge Platteel and {de Jong}, {Koert P.} and Grietje Molema",
year = "2008",
month = "11",
doi = "10.1002/hep.22490",
language = "English",
volume = "48",
pages = "1517--1527",
journal = "Hepatology",
issn = "0270-9139",
publisher = "WILEY",
number = "5",

}

RIS

TY - JOUR

T1 - The Angiogenic Makeup of Human Hepatocellular Carcinoma Does Not Favor Vascular Endothelial Growth Factor/Angiopoletin-Driven Sprouting Neovascularization

AU - Zeng, Wenjiao

AU - Gouw, Annette S. H.

AU - van den Heuvel, Marius C.

AU - Zwiers, Peter J.

AU - Zondervan, Pieter E.

AU - Poppema, Sibrand

AU - Zhang, Nong

AU - Platteel, Inge

AU - de Jong, Koert P.

AU - Molema, Grietje

PY - 2008/11

Y1 - 2008/11

N2 - Quantitative data on the expression of multiple factors that control angiogenesis in hepatocellular carcinoma (HCC) are limited. A better understanding of the mechanisms underlying angiogenesis in HCC will improve the rational choice of anti-angiogenic treatment. We quantified gene and protein expression of members of the vascular endothelial growth factor (VEGF) and angiopoietin systems and studied localization of VEGF, its receptors VEGFR-1 and VEGFR-2, Angiopoietin (Ang)-1 and Ang-2, and their receptor, in HCC in noncirrhotic and cirrhotic livers. We employed real-time reverse transcription polymerase chain reaction (RT-PCR), western blot, and immunohistology, and compared the outcome with highly angiogenic human renal cell carcinoma (RCC). HCC in noncirrhotic and cirrhotic livers expressed VEGF and its receptors to a similar extent as normal liver, although in cirrhotic background, VEGFR-2 levels in both tumor and adjacent tissue were decreased. Ang-1 expression was slightly increased compared with normal liver, whereas Tie-2 was strongly down-regulated in the tumor vasculature. Ang-2 messenger RNA (mRNA) levels were also low in HCCs of both noncirrhotic and cirrhotic livers, implying that VEGF-driven angiogenic sprouting accompanied by angiopoietin-driven vascular destabilization is not pronounced. In RCC, VEGF-A levels were one order of magnitude higher. At the same time, endothelially expressed Ang-2 was over 30-fold increased compared with expression in normal kidney, whereas Ang-1 expression was decreased. Conclusion: In hepatocellular carcinoma, tumor vascularization is not per se VEGF/angiopoietin driven. However, increased CD31 expression and morphological changes representative of sinusoidal capillarization in tumor vasculature indicate that vascular remodeling is taking place. This portends that therapeutic intervention of HCC at the level of the vasculature is optional, and that further studies into the molecular control thereof are warranted. (HEPATOLOGY 2008;48: 1517-1527.)

AB - Quantitative data on the expression of multiple factors that control angiogenesis in hepatocellular carcinoma (HCC) are limited. A better understanding of the mechanisms underlying angiogenesis in HCC will improve the rational choice of anti-angiogenic treatment. We quantified gene and protein expression of members of the vascular endothelial growth factor (VEGF) and angiopoietin systems and studied localization of VEGF, its receptors VEGFR-1 and VEGFR-2, Angiopoietin (Ang)-1 and Ang-2, and their receptor, in HCC in noncirrhotic and cirrhotic livers. We employed real-time reverse transcription polymerase chain reaction (RT-PCR), western blot, and immunohistology, and compared the outcome with highly angiogenic human renal cell carcinoma (RCC). HCC in noncirrhotic and cirrhotic livers expressed VEGF and its receptors to a similar extent as normal liver, although in cirrhotic background, VEGFR-2 levels in both tumor and adjacent tissue were decreased. Ang-1 expression was slightly increased compared with normal liver, whereas Tie-2 was strongly down-regulated in the tumor vasculature. Ang-2 messenger RNA (mRNA) levels were also low in HCCs of both noncirrhotic and cirrhotic livers, implying that VEGF-driven angiogenic sprouting accompanied by angiopoietin-driven vascular destabilization is not pronounced. In RCC, VEGF-A levels were one order of magnitude higher. At the same time, endothelially expressed Ang-2 was over 30-fold increased compared with expression in normal kidney, whereas Ang-1 expression was decreased. Conclusion: In hepatocellular carcinoma, tumor vascularization is not per se VEGF/angiopoietin driven. However, increased CD31 expression and morphological changes representative of sinusoidal capillarization in tumor vasculature indicate that vascular remodeling is taking place. This portends that therapeutic intervention of HCC at the level of the vasculature is optional, and that further studies into the molecular control thereof are warranted. (HEPATOLOGY 2008;48: 1517-1527.)

KW - RENAL-CELL CARCINOMA

KW - ANTIANGIOGENIC THERAPY

KW - COLORECTAL-CANCER

KW - LIVER METASTASES

KW - GENE-EXPRESSION

KW - FACTOR RECEPTOR

KW - OVEREXPRESSION

KW - ANGIOPOIETIN-2

KW - APOPTOSIS

KW - QUANTIFICATION

U2 - 10.1002/hep.22490

DO - 10.1002/hep.22490

M3 - Article

VL - 48

SP - 1517

EP - 1527

JO - Hepatology

JF - Hepatology

SN - 0270-9139

IS - 5

ER -

ID: 4800172