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IL-1β Promotes Vasculogenic Mimicry of Breast Cancer Cells Through p38/MAPK and PI3K/Akt Signaling Pathways
Vasculogenic mimicry (VM), a micro vessel-like structure formed by the cancer cells, plays a pivotal role in cancer malignancy and progression. Interleukin-1 beta (IL-1β) is an active pro-inflammatory cytokine and elevated in many tumor types, including breast cancer. However, the effect of IL-1β on...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8160375/ https://www.ncbi.nlm.nih.gov/pubmed/34055597 http://dx.doi.org/10.3389/fonc.2021.618839 |
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author | Nisar, Muhammad Azhar Zheng, Qin Saleem, Muhammad Zubair Ahmmed, Bulbul Ramzan, Muhammad Noman Ud Din, Syed Riaz Tahir, Naeem Liu, Shuai Yan, Qiu |
author_facet | Nisar, Muhammad Azhar Zheng, Qin Saleem, Muhammad Zubair Ahmmed, Bulbul Ramzan, Muhammad Noman Ud Din, Syed Riaz Tahir, Naeem Liu, Shuai Yan, Qiu |
author_sort | Nisar, Muhammad Azhar |
collection | PubMed |
description | Vasculogenic mimicry (VM), a micro vessel-like structure formed by the cancer cells, plays a pivotal role in cancer malignancy and progression. Interleukin-1 beta (IL-1β) is an active pro-inflammatory cytokine and elevated in many tumor types, including breast cancer. However, the effect of IL-1β on the VM of breast cancer has not been clearly elucidated. In this study, breast cancer cells (MCF-7 and MDA-MB-231) were used to study the effect of IL-1β on the changes that can promote VM. The evidence for VM stimulated by IL-1β was acquired by analyzing the expression of VM-associated biomarkers (VE-cadherin, VEGFR-1, MMP-9, MMP-2, c-Fos, and c-Jun) via western blot, immunofluorescent staining, and Immunohistochemistry (IHC). Additionally, morphological evidence was collected via Matrigel-based cord formation assay under normoxic/hypoxic conditions and microvessel examination through Hematoxylin and Eosin staining (H&E). Furthermore, the STRING and Gene Ontology database was also used to analyze the VM-associated interacting molecules stimulated by IL-β. The results showed that the expression of VM biomarkers was increased in both MCF-7 and MDA-MB-231 cells after IL-1β treatment. The increase in VM response was observed in IL-1β treated cells under both normoxia and hypoxia. IL-1β also increased the activation of transcription factor AP-1 complex (c-Fos/c-Jun). The bioinformatics data indicated that p38/MAPK and PI3K/Akt signaling pathways were involved in the IL-1β stimulation. It was further confirmed by the downregulated expression of VM biomarkers and reduced formation of the intersections upon the addition of the signaling pathway inhibitors. The study suggests that IL-1β stimulates the VM and its associated events in breast cancer cells via p38/MAPK and PI3K/Akt signaling pathways. Aiming the VM-associated molecular targets promoted by IL-1β may offer a novel anti-angiogenic therapeutic strategy to control the aggressiveness of breast cancer cells. |
format | Online Article Text |
id | pubmed-8160375 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-81603752021-05-29 IL-1β Promotes Vasculogenic Mimicry of Breast Cancer Cells Through p38/MAPK and PI3K/Akt Signaling Pathways Nisar, Muhammad Azhar Zheng, Qin Saleem, Muhammad Zubair Ahmmed, Bulbul Ramzan, Muhammad Noman Ud Din, Syed Riaz Tahir, Naeem Liu, Shuai Yan, Qiu Front Oncol Oncology Vasculogenic mimicry (VM), a micro vessel-like structure formed by the cancer cells, plays a pivotal role in cancer malignancy and progression. Interleukin-1 beta (IL-1β) is an active pro-inflammatory cytokine and elevated in many tumor types, including breast cancer. However, the effect of IL-1β on the VM of breast cancer has not been clearly elucidated. In this study, breast cancer cells (MCF-7 and MDA-MB-231) were used to study the effect of IL-1β on the changes that can promote VM. The evidence for VM stimulated by IL-1β was acquired by analyzing the expression of VM-associated biomarkers (VE-cadherin, VEGFR-1, MMP-9, MMP-2, c-Fos, and c-Jun) via western blot, immunofluorescent staining, and Immunohistochemistry (IHC). Additionally, morphological evidence was collected via Matrigel-based cord formation assay under normoxic/hypoxic conditions and microvessel examination through Hematoxylin and Eosin staining (H&E). Furthermore, the STRING and Gene Ontology database was also used to analyze the VM-associated interacting molecules stimulated by IL-β. The results showed that the expression of VM biomarkers was increased in both MCF-7 and MDA-MB-231 cells after IL-1β treatment. The increase in VM response was observed in IL-1β treated cells under both normoxia and hypoxia. IL-1β also increased the activation of transcription factor AP-1 complex (c-Fos/c-Jun). The bioinformatics data indicated that p38/MAPK and PI3K/Akt signaling pathways were involved in the IL-1β stimulation. It was further confirmed by the downregulated expression of VM biomarkers and reduced formation of the intersections upon the addition of the signaling pathway inhibitors. The study suggests that IL-1β stimulates the VM and its associated events in breast cancer cells via p38/MAPK and PI3K/Akt signaling pathways. Aiming the VM-associated molecular targets promoted by IL-1β may offer a novel anti-angiogenic therapeutic strategy to control the aggressiveness of breast cancer cells. Frontiers Media S.A. 2021-05-14 /pmc/articles/PMC8160375/ /pubmed/34055597 http://dx.doi.org/10.3389/fonc.2021.618839 Text en Copyright © 2021 Nisar, Zheng, Saleem, Ahmmed, Ramzan, Ud Din, Tahir, Liu and Yan. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Oncology Nisar, Muhammad Azhar Zheng, Qin Saleem, Muhammad Zubair Ahmmed, Bulbul Ramzan, Muhammad Noman Ud Din, Syed Riaz Tahir, Naeem Liu, Shuai Yan, Qiu IL-1β Promotes Vasculogenic Mimicry of Breast Cancer Cells Through p38/MAPK and PI3K/Akt Signaling Pathways |
title | IL-1β Promotes Vasculogenic Mimicry of Breast Cancer Cells Through p38/MAPK and PI3K/Akt Signaling Pathways |
title_full | IL-1β Promotes Vasculogenic Mimicry of Breast Cancer Cells Through p38/MAPK and PI3K/Akt Signaling Pathways |
title_fullStr | IL-1β Promotes Vasculogenic Mimicry of Breast Cancer Cells Through p38/MAPK and PI3K/Akt Signaling Pathways |
title_full_unstemmed | IL-1β Promotes Vasculogenic Mimicry of Breast Cancer Cells Through p38/MAPK and PI3K/Akt Signaling Pathways |
title_short | IL-1β Promotes Vasculogenic Mimicry of Breast Cancer Cells Through p38/MAPK and PI3K/Akt Signaling Pathways |
title_sort | il-1β promotes vasculogenic mimicry of breast cancer cells through p38/mapk and pi3k/akt signaling pathways |
topic | Oncology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8160375/ https://www.ncbi.nlm.nih.gov/pubmed/34055597 http://dx.doi.org/10.3389/fonc.2021.618839 |
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