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

doi:10.3892/etm.2021.10032

Role of Notch, IL‑1 and leptin expression in colorectal cancer

Authors:
- Nilufer Erkasap
- Rumeysa Ozyurt
- Mete Ozkurt
- Serdar Erkasap
- Fatih Yasar
- Enver Ihtiyar
- Evrim Ciftci
- Funda Canaz
- Ertugrul Colak
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Affiliations: Department of Physiology, Eskisehir Osmangazi University Medical Faculty, Odunpazari, Eskisehir 26040, Turkey, Department of General Surgery, Eskisehir Osmangazi University Medical Faculty, Odunpazari, Eskisehir 26040, Turkey, Department of Pathology, Eskisehir Osmangazi University Medical Faculty, Odunpazari, Eskisehir 26040, Turkey, Department of Biostatistics, Eskisehir Osmangazi University Medical Faculty, Odunpazari, Eskisehir 26040, Turkey
Published online on: April 11, 2021 https://doi.org/10.3892/etm.2021.10032
Article Number: 600
Copyright: © Erkasap et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

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.

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