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Arterio-venous gradients of IL-6, plasma and serum VEGF and D-dimers in human cancer

The circulating angiogenic factors vascular endothelial growth factor-A, interleukin-6 and the fibrin D-dimer fragment were measured in the mesenteric vein, the uterine vein, as well as in peripheral venous and arterial samples in 21 randomly selected patients with operable colorectal, ovarian and c...

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Autores principales: Salgado, R, Benoy, I, Weytjens, R, Van Bockstaele, D, Van Marck, E, Huget, Ph, Hoylaerts, M, Vermeulen, P, Dirix, L Y
Formato: Texto
Lenguaje:English
Publicado: Nature Publishing Group 2002
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2376277/
https://www.ncbi.nlm.nih.gov/pubmed/12454774
http://dx.doi.org/10.1038/sj.bjc.6600655
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author Salgado, R
Benoy, I
Weytjens, R
Van Bockstaele, D
Van Marck, E
Huget, Ph
Hoylaerts, M
Vermeulen, P
Dirix, L Y
author_facet Salgado, R
Benoy, I
Weytjens, R
Van Bockstaele, D
Van Marck, E
Huget, Ph
Hoylaerts, M
Vermeulen, P
Dirix, L Y
author_sort Salgado, R
collection PubMed
description The circulating angiogenic factors vascular endothelial growth factor-A, interleukin-6 and the fibrin D-dimer fragment were measured in the mesenteric vein, the uterine vein, as well as in peripheral venous and arterial samples in 21 randomly selected patients with operable colorectal, ovarian and cervical carcinoma. In addition, immunohistochemistry for vascular endothelial growth factor-A and interleukin-6 was performed on colorectal tumours of such patients. Serum and plasma vascular endothelial growth factor-A were not significantly elevated in the vein draining the tumours, despite tumour cell expression of vascular endothelial growth factor-A. Serum vascular endothelial growth factor-A is therefore not all tumour-derived. In contrast, serum interleukin-6 was highly elevated in the draining veins in agreement with expression of interleukin-6 in the cytoplasm of tumour cells. In the megakaryoblastic cell line MEG-01, the expression of vascular endothelial growth factor-A was found to be regulated by interleukin-6. Thus, the higher platelet vascular endothelial growth factor-A load resulting in higher serum vascular endothelial growth factor levels in cancer patients may partly result from an interleukin-6 mediated up-regulation of the expression of vascular endothelial growth factor-A in the precursor of the platelet, i.e. the megakaryocyte. We also confirmed by immunohistochemistry that platelets adhere and aggregate on tumour endothelium. We propose that interleukin-6 indirectly promotes tumour angiogenesis through its up-regulation of the vascular endothelial growth factor-A load in platelets. In addition, the correlations found between peripheral venous interleukin-6 and peripheral venous fibrinogen and D-dimers levels, and the high D-dimer levels found in the draining vein of the tumour, in agreement with fibrin deposits found in the tumour stroma, suggest an important role for interleukin-6 in extra-vascular fibrinogen metabolism. Our results suggest a pivotal role for interleukin-6 in the intrinsic link between haemostasis and angiogenesis. This might be of importance in the development of anti-angiogenic agents based on interference with haemostasis. British Journal of Cancer (2002) 87, 1437–1444. doi:10.1038/sj.bjc.6600655 www.bjcancer.com © 2002 Cancer Research UK
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spelling pubmed-23762772009-09-10 Arterio-venous gradients of IL-6, plasma and serum VEGF and D-dimers in human cancer Salgado, R Benoy, I Weytjens, R Van Bockstaele, D Van Marck, E Huget, Ph Hoylaerts, M Vermeulen, P Dirix, L Y Br J Cancer Molecular and Cellular Pathology The circulating angiogenic factors vascular endothelial growth factor-A, interleukin-6 and the fibrin D-dimer fragment were measured in the mesenteric vein, the uterine vein, as well as in peripheral venous and arterial samples in 21 randomly selected patients with operable colorectal, ovarian and cervical carcinoma. In addition, immunohistochemistry for vascular endothelial growth factor-A and interleukin-6 was performed on colorectal tumours of such patients. Serum and plasma vascular endothelial growth factor-A were not significantly elevated in the vein draining the tumours, despite tumour cell expression of vascular endothelial growth factor-A. Serum vascular endothelial growth factor-A is therefore not all tumour-derived. In contrast, serum interleukin-6 was highly elevated in the draining veins in agreement with expression of interleukin-6 in the cytoplasm of tumour cells. In the megakaryoblastic cell line MEG-01, the expression of vascular endothelial growth factor-A was found to be regulated by interleukin-6. Thus, the higher platelet vascular endothelial growth factor-A load resulting in higher serum vascular endothelial growth factor levels in cancer patients may partly result from an interleukin-6 mediated up-regulation of the expression of vascular endothelial growth factor-A in the precursor of the platelet, i.e. the megakaryocyte. We also confirmed by immunohistochemistry that platelets adhere and aggregate on tumour endothelium. We propose that interleukin-6 indirectly promotes tumour angiogenesis through its up-regulation of the vascular endothelial growth factor-A load in platelets. In addition, the correlations found between peripheral venous interleukin-6 and peripheral venous fibrinogen and D-dimers levels, and the high D-dimer levels found in the draining vein of the tumour, in agreement with fibrin deposits found in the tumour stroma, suggest an important role for interleukin-6 in extra-vascular fibrinogen metabolism. Our results suggest a pivotal role for interleukin-6 in the intrinsic link between haemostasis and angiogenesis. This might be of importance in the development of anti-angiogenic agents based on interference with haemostasis. British Journal of Cancer (2002) 87, 1437–1444. doi:10.1038/sj.bjc.6600655 www.bjcancer.com © 2002 Cancer Research UK Nature Publishing Group 2002-12-02 2002-12-02 /pmc/articles/PMC2376277/ /pubmed/12454774 http://dx.doi.org/10.1038/sj.bjc.6600655 Text en Copyright © 2002 Cancer Research UK https://creativecommons.org/licenses/by/4.0/This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material.If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit https://creativecommons.org/licenses/by/4.0/.
spellingShingle Molecular and Cellular Pathology
Salgado, R
Benoy, I
Weytjens, R
Van Bockstaele, D
Van Marck, E
Huget, Ph
Hoylaerts, M
Vermeulen, P
Dirix, L Y
Arterio-venous gradients of IL-6, plasma and serum VEGF and D-dimers in human cancer
title Arterio-venous gradients of IL-6, plasma and serum VEGF and D-dimers in human cancer
title_full Arterio-venous gradients of IL-6, plasma and serum VEGF and D-dimers in human cancer
title_fullStr Arterio-venous gradients of IL-6, plasma and serum VEGF and D-dimers in human cancer
title_full_unstemmed Arterio-venous gradients of IL-6, plasma and serum VEGF and D-dimers in human cancer
title_short Arterio-venous gradients of IL-6, plasma and serum VEGF and D-dimers in human cancer
title_sort arterio-venous gradients of il-6, plasma and serum vegf and d-dimers in human cancer
topic Molecular and Cellular Pathology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2376277/
https://www.ncbi.nlm.nih.gov/pubmed/12454774
http://dx.doi.org/10.1038/sj.bjc.6600655
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