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Human endothelial cells promote arsenic-transformed lung epithelial cells to induce tumor growth and angiogenesis through interleukin-8 induction

Arsenic exposure is associated with lung cancer. Angiogenesis is essential for tumor development. However, the role and mechanism of human vascular endothelial cells in tumor growth and angiogenesis induced by arsenic-transformed bronchial epithelial (As-T) cells remain to be elucidated. In this stu...

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Autores principales: Zhao, Lei, Wang, Yi-Fang, Liu, Jie, Jiang, Bing-Hua, Liu, Ling-Zhi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8954972/
https://www.ncbi.nlm.nih.gov/pubmed/35241635
http://dx.doi.org/10.18632/aging.203930
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author Zhao, Lei
Wang, Yi-Fang
Liu, Jie
Jiang, Bing-Hua
Liu, Ling-Zhi
author_facet Zhao, Lei
Wang, Yi-Fang
Liu, Jie
Jiang, Bing-Hua
Liu, Ling-Zhi
author_sort Zhao, Lei
collection PubMed
description Arsenic exposure is associated with lung cancer. Angiogenesis is essential for tumor development. However, the role and mechanism of human vascular endothelial cells in tumor growth and angiogenesis induced by arsenic-transformed bronchial epithelial (As-T) cells remain to be elucidated. In this study, we found that endothelial cells significantly increased As-T cell-induced tumor growth compared to those induced by As-T cells alone. To understand the molecular mechanism, we found that endothelial cells co-cultured with As-T cells or cultured in conditioned medium (CM) prepared from As-T cells showed much higher cell migration, proliferation, and tube formation compared to those co-cultured with BEAS-2B (B2B) cells or cultured in CM from B2B. We identified that higher levels of intracellular interleukin 8 (IL-8) were secreted by As-T cells, which activated IL-8/IL-8R signaling to promote endothelial cells migration and tube formation. IL-8 silencing and knockout (KO) in As-T cells, or IL-8 neutralizing antibody dramatically suppressed endothelial cell proliferation, migration, tube formation in vitro, and tumor growth and angiogenesis in vivo, suggesting a key role of IL-8 in As-T cells to induce angiogenesis via a paracrine effect. Finally, blocking of IL-8 receptors C-X-C chemokine receptor type 1 (CXCR1) and CXCR2 with neutralizing antibodies and chemical inhibitors inhibited tube formation, indicating that IL-8Rs on endothelial cells are necessary for As-T cell-induced angiogenesis. Overall, this study reveals an important molecular mechanism of arsenic-induced carcinogenesis, and suggests a new option to prevent and treat arsenic-induced angiogenesis.
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spelling pubmed-89549722022-03-28 Human endothelial cells promote arsenic-transformed lung epithelial cells to induce tumor growth and angiogenesis through interleukin-8 induction Zhao, Lei Wang, Yi-Fang Liu, Jie Jiang, Bing-Hua Liu, Ling-Zhi Aging (Albany NY) Research Paper Arsenic exposure is associated with lung cancer. Angiogenesis is essential for tumor development. However, the role and mechanism of human vascular endothelial cells in tumor growth and angiogenesis induced by arsenic-transformed bronchial epithelial (As-T) cells remain to be elucidated. In this study, we found that endothelial cells significantly increased As-T cell-induced tumor growth compared to those induced by As-T cells alone. To understand the molecular mechanism, we found that endothelial cells co-cultured with As-T cells or cultured in conditioned medium (CM) prepared from As-T cells showed much higher cell migration, proliferation, and tube formation compared to those co-cultured with BEAS-2B (B2B) cells or cultured in CM from B2B. We identified that higher levels of intracellular interleukin 8 (IL-8) were secreted by As-T cells, which activated IL-8/IL-8R signaling to promote endothelial cells migration and tube formation. IL-8 silencing and knockout (KO) in As-T cells, or IL-8 neutralizing antibody dramatically suppressed endothelial cell proliferation, migration, tube formation in vitro, and tumor growth and angiogenesis in vivo, suggesting a key role of IL-8 in As-T cells to induce angiogenesis via a paracrine effect. Finally, blocking of IL-8 receptors C-X-C chemokine receptor type 1 (CXCR1) and CXCR2 with neutralizing antibodies and chemical inhibitors inhibited tube formation, indicating that IL-8Rs on endothelial cells are necessary for As-T cell-induced angiogenesis. Overall, this study reveals an important molecular mechanism of arsenic-induced carcinogenesis, and suggests a new option to prevent and treat arsenic-induced angiogenesis. Impact Journals 2022-03-03 /pmc/articles/PMC8954972/ /pubmed/35241635 http://dx.doi.org/10.18632/aging.203930 Text en Copyright: © 2022 Zhao et al. https://creativecommons.org/licenses/by/3.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/3.0/) (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Zhao, Lei
Wang, Yi-Fang
Liu, Jie
Jiang, Bing-Hua
Liu, Ling-Zhi
Human endothelial cells promote arsenic-transformed lung epithelial cells to induce tumor growth and angiogenesis through interleukin-8 induction
title Human endothelial cells promote arsenic-transformed lung epithelial cells to induce tumor growth and angiogenesis through interleukin-8 induction
title_full Human endothelial cells promote arsenic-transformed lung epithelial cells to induce tumor growth and angiogenesis through interleukin-8 induction
title_fullStr Human endothelial cells promote arsenic-transformed lung epithelial cells to induce tumor growth and angiogenesis through interleukin-8 induction
title_full_unstemmed Human endothelial cells promote arsenic-transformed lung epithelial cells to induce tumor growth and angiogenesis through interleukin-8 induction
title_short Human endothelial cells promote arsenic-transformed lung epithelial cells to induce tumor growth and angiogenesis through interleukin-8 induction
title_sort human endothelial cells promote arsenic-transformed lung epithelial cells to induce tumor growth and angiogenesis through interleukin-8 induction
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8954972/
https://www.ncbi.nlm.nih.gov/pubmed/35241635
http://dx.doi.org/10.18632/aging.203930
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