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Increased endothelin-1 in colorectal cancer and reduction of tumour growth by ET (A) receptor antagonism
Endothelin-1 (ET-1) is a vasoconstrictor peptide which stimulates proliferation in vitro in different cell types, including colorectal cancer cells. Raised ET-1 levels have been detected both on tissue specimens and in the plasma of patients with cancers. To investigate the role of ET-1 in colorecta...
Autores principales: | , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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Nature Publishing Group
2001
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2363991/ https://www.ncbi.nlm.nih.gov/pubmed/11742499 http://dx.doi.org/10.1054/bjoc.2001.2193 |
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author | Asham, E Shankar, A Loizidou, M Fredericks, S Miller, K Boulos, P B Burnstock, G Taylor, I |
author_facet | Asham, E Shankar, A Loizidou, M Fredericks, S Miller, K Boulos, P B Burnstock, G Taylor, I |
author_sort | Asham, E |
collection | PubMed |
description | Endothelin-1 (ET-1) is a vasoconstrictor peptide which stimulates proliferation in vitro in different cell types, including colorectal cancer cells. Raised ET-1 levels have been detected both on tissue specimens and in the plasma of patients with cancers. To investigate the role of ET-1 in colorectal cancer: (i) ET-1 plasma levels in patients with colorectal cancer were measured by radioimmunoassay: group 1 = controls (n = 22), group 2 = primary colorectal cancer only (n = 39), group 3 = liver metastases only (n = 26); (ii) ET-1 expression in primary colorectal cancer specimens (n =10) was determined immunohistochemically and (iii) the effect of intraportally infused antagonists to the two ET-1 receptors, ET (A) and ET (B), on the growth of liver metastases in a rat model was assessed. ET-1 plasma levels were significantly increased in both patients with primary tumour and patients with metastases, compared to controls (P < 0.01, 3.9 ± 1.4, 4.5 ± 1.5, vs. 2.75 ± 1.37 pg/ml, respectively). Immunohistochemically, strong expression of ET-1 was found in the cytoplasm, stroma and blood vessels of cancers, unlike the normal colon where only the apical layer of the epithelium, vascular endothelial cells and surrounding stroma were positively stained. In the rat model, there was significant reduction in liver tumour weights compared to controls, following treatment with the ET (A) antagonist (BQ123) 30 min after the intraportal inoculation of tumour cells (P < 0.05). These results suggest ET-1 is produced by colorectal cancers and may play a role in the growth of colorectal cancer acting through ET (A) receptors. ET (A) antagonists are indicated as potential anti-cancer agents. © 2001 Cancer Research Campaign http://www.bjcancer.com |
format | Text |
id | pubmed-2363991 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2001 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-23639912009-09-10 Increased endothelin-1 in colorectal cancer and reduction of tumour growth by ET (A) receptor antagonism Asham, E Shankar, A Loizidou, M Fredericks, S Miller, K Boulos, P B Burnstock, G Taylor, I Br J Cancer Regular Article Endothelin-1 (ET-1) is a vasoconstrictor peptide which stimulates proliferation in vitro in different cell types, including colorectal cancer cells. Raised ET-1 levels have been detected both on tissue specimens and in the plasma of patients with cancers. To investigate the role of ET-1 in colorectal cancer: (i) ET-1 plasma levels in patients with colorectal cancer were measured by radioimmunoassay: group 1 = controls (n = 22), group 2 = primary colorectal cancer only (n = 39), group 3 = liver metastases only (n = 26); (ii) ET-1 expression in primary colorectal cancer specimens (n =10) was determined immunohistochemically and (iii) the effect of intraportally infused antagonists to the two ET-1 receptors, ET (A) and ET (B), on the growth of liver metastases in a rat model was assessed. ET-1 plasma levels were significantly increased in both patients with primary tumour and patients with metastases, compared to controls (P < 0.01, 3.9 ± 1.4, 4.5 ± 1.5, vs. 2.75 ± 1.37 pg/ml, respectively). Immunohistochemically, strong expression of ET-1 was found in the cytoplasm, stroma and blood vessels of cancers, unlike the normal colon where only the apical layer of the epithelium, vascular endothelial cells and surrounding stroma were positively stained. In the rat model, there was significant reduction in liver tumour weights compared to controls, following treatment with the ET (A) antagonist (BQ123) 30 min after the intraportal inoculation of tumour cells (P < 0.05). These results suggest ET-1 is produced by colorectal cancers and may play a role in the growth of colorectal cancer acting through ET (A) receptors. ET (A) antagonists are indicated as potential anti-cancer agents. © 2001 Cancer Research Campaign http://www.bjcancer.com Nature Publishing Group 2001-11 /pmc/articles/PMC2363991/ /pubmed/11742499 http://dx.doi.org/10.1054/bjoc.2001.2193 Text en Copyright © 2001 Cancer Research Campaign 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 | Regular Article Asham, E Shankar, A Loizidou, M Fredericks, S Miller, K Boulos, P B Burnstock, G Taylor, I Increased endothelin-1 in colorectal cancer and reduction of tumour growth by ET (A) receptor antagonism |
title | Increased endothelin-1 in colorectal cancer and reduction of tumour growth by ET (A) receptor antagonism |
title_full | Increased endothelin-1 in colorectal cancer and reduction of tumour growth by ET (A) receptor antagonism |
title_fullStr | Increased endothelin-1 in colorectal cancer and reduction of tumour growth by ET (A) receptor antagonism |
title_full_unstemmed | Increased endothelin-1 in colorectal cancer and reduction of tumour growth by ET (A) receptor antagonism |
title_short | Increased endothelin-1 in colorectal cancer and reduction of tumour growth by ET (A) receptor antagonism |
title_sort | increased endothelin-1 in colorectal cancer and reduction of tumour growth by et (a) receptor antagonism |
topic | Regular Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2363991/ https://www.ncbi.nlm.nih.gov/pubmed/11742499 http://dx.doi.org/10.1054/bjoc.2001.2193 |
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