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Role of Notch, IL-1 and leptin expression in colorectal cancer
An increasing number of studies have shown that angiogenesis has an important role in the progression of cancer. The growth of a new network of blood vessels is crucial for tumor growth and metastasis, which is promoted by several proangiogenic factors. Leptin, an essential adipokine that is secrete...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
D.A. Spandidos
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8056113/ https://www.ncbi.nlm.nih.gov/pubmed/33884038 http://dx.doi.org/10.3892/etm.2021.10032 |
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author | Erkasap, Nilufer Ozyurt, Rumeysa Ozkurt, Mete Erkasap, Serdar Yasar, Fatih Ihtiyar, Enver Ciftci, Evrim Canaz, Funda Colak, Ertugrul |
author_facet | Erkasap, Nilufer Ozyurt, Rumeysa Ozkurt, Mete Erkasap, Serdar Yasar, Fatih Ihtiyar, Enver Ciftci, Evrim Canaz, Funda Colak, Ertugrul |
author_sort | Erkasap, Nilufer |
collection | PubMed |
description | An increasing number of studies have shown that angiogenesis has an important role in the progression of cancer. The growth of a new network of blood vessels is crucial for tumor growth and metastasis, which is promoted by several proangiogenic factors. Leptin, an essential adipokine that is secreted from fat tissue, is one of these pro-angiogenic factors. It has been shown that the inhibition of leptin-induced angiogenesis resulted in decreased levels of vascular endothelial growth factor (VEGF)/VEGFR2, hypoxia inducible factor (HIF) 1α, NF-κB, IL-1 and Notch and reduced the tumor growth in breast cancer. Leptin induces angiogenesis in breast cancer either by upregulating VEGFR2 in endothelial cells or by increasing VEGF/VEGFR2 expression through the Notch, IL-1 and leptin crosstalk outcome (NILCO) pathway. NILCO is a novel mechanism that interacts with proinflammatory and proangiogenic signals, which are critical for cell proliferation and angiogenesis in cancer. Several studies have shown that components of NILCO may affect human cancer incidence and progression. However, to the best of our knowledge, the interactions between Notch, IL-1 and leptin in human colorectal cancer have not been yet studied at the molecular level. The aim of the present study was to investigate the expression levels of genes related to the NILCO pathway in human colorectal cancer specimens. The current results demonstrated that leptin, leptin receptor (ObR) b, Notch-1, Notch-4, IL-1α, IL-1β, IL-1R, IL-6, JAK-2, STAT-1, STAT-3, VEGFA, VEGFR1, VEGFR2, TNF-α and NF-κB mRNA expression levels in the cancer tissue were increased compared with the normal tissue. No significant changes in the mRNA expression levels of Jagged-1, HIF-1α and TNF receptor 1 were observed. Western blotting revealed that the protein expression levels of IκB were increased in the cancer tissue compared with normal tissue, whereas HIF-1α and phosphorylated STAT-1 levels were decreased. IL-6 and VEGFA plasma concentrations were statistically raised and the leptin plasma concentration was also raised, although significantly, patients with cancer compared with control individuals. Together, the present findings indicated that Notch, IL-1 and leptin may serve a crucial role in the development of colorectal cancer. |
format | Online Article Text |
id | pubmed-8056113 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | D.A. Spandidos |
record_format | MEDLINE/PubMed |
spelling | pubmed-80561132021-04-20 Role of Notch, IL-1 and leptin expression in colorectal cancer Erkasap, Nilufer Ozyurt, Rumeysa Ozkurt, Mete Erkasap, Serdar Yasar, Fatih Ihtiyar, Enver Ciftci, Evrim Canaz, Funda Colak, Ertugrul Exp Ther Med Articles An increasing number of studies have shown that angiogenesis has an important role in the progression of cancer. The growth of a new network of blood vessels is crucial for tumor growth and metastasis, which is promoted by several proangiogenic factors. Leptin, an essential adipokine that is secreted from fat tissue, is one of these pro-angiogenic factors. It has been shown that the inhibition of leptin-induced angiogenesis resulted in decreased levels of vascular endothelial growth factor (VEGF)/VEGFR2, hypoxia inducible factor (HIF) 1α, NF-κB, IL-1 and Notch and reduced the tumor growth in breast cancer. Leptin induces angiogenesis in breast cancer either by upregulating VEGFR2 in endothelial cells or by increasing VEGF/VEGFR2 expression through the Notch, IL-1 and leptin crosstalk outcome (NILCO) pathway. NILCO is a novel mechanism that interacts with proinflammatory and proangiogenic signals, which are critical for cell proliferation and angiogenesis in cancer. Several studies have shown that components of NILCO may affect human cancer incidence and progression. However, to the best of our knowledge, the interactions between Notch, IL-1 and leptin in human colorectal cancer have not been yet studied at the molecular level. The aim of the present study was to investigate the expression levels of genes related to the NILCO pathway in human colorectal cancer specimens. The current results demonstrated that leptin, leptin receptor (ObR) b, Notch-1, Notch-4, IL-1α, IL-1β, IL-1R, IL-6, JAK-2, STAT-1, STAT-3, VEGFA, VEGFR1, VEGFR2, TNF-α and NF-κB mRNA expression levels in the cancer tissue were increased compared with the normal tissue. No significant changes in the mRNA expression levels of Jagged-1, HIF-1α and TNF receptor 1 were observed. Western blotting revealed that the protein expression levels of IκB were increased in the cancer tissue compared with normal tissue, whereas HIF-1α and phosphorylated STAT-1 levels were decreased. IL-6 and VEGFA plasma concentrations were statistically raised and the leptin plasma concentration was also raised, although significantly, patients with cancer compared with control individuals. Together, the present findings indicated that Notch, IL-1 and leptin may serve a crucial role in the development of colorectal cancer. D.A. Spandidos 2021-06 2021-04-11 /pmc/articles/PMC8056113/ /pubmed/33884038 http://dx.doi.org/10.3892/etm.2021.10032 Text en Copyright: © Erkasap et al. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. |
spellingShingle | Articles Erkasap, Nilufer Ozyurt, Rumeysa Ozkurt, Mete Erkasap, Serdar Yasar, Fatih Ihtiyar, Enver Ciftci, Evrim Canaz, Funda Colak, Ertugrul Role of Notch, IL-1 and leptin expression in colorectal cancer |
title | Role of Notch, IL-1 and leptin expression in colorectal cancer |
title_full | Role of Notch, IL-1 and leptin expression in colorectal cancer |
title_fullStr | Role of Notch, IL-1 and leptin expression in colorectal cancer |
title_full_unstemmed | Role of Notch, IL-1 and leptin expression in colorectal cancer |
title_short | Role of Notch, IL-1 and leptin expression in colorectal cancer |
title_sort | role of notch, il-1 and leptin expression in colorectal cancer |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8056113/ https://www.ncbi.nlm.nih.gov/pubmed/33884038 http://dx.doi.org/10.3892/etm.2021.10032 |
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