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Cxcr1 mediates recruitment of neutrophils and supports proliferation of tumor-initiating astrocytes in vivo

Neutrophils are first-responders to sites of infection and tissue damage including the inflamed tumor microenvironment. Increasing evidence suggests that crosstalk between tumors and neutrophils can affect the progression of established tumors. However, there is a gap in our understanding of the ear...

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Autores principales: Powell, Davalyn, Lou, Meng, Barros Becker, Francisco, Huttenlocher, Anna
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6125480/
https://www.ncbi.nlm.nih.gov/pubmed/30185911
http://dx.doi.org/10.1038/s41598-018-31675-0
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author Powell, Davalyn
Lou, Meng
Barros Becker, Francisco
Huttenlocher, Anna
author_facet Powell, Davalyn
Lou, Meng
Barros Becker, Francisco
Huttenlocher, Anna
author_sort Powell, Davalyn
collection PubMed
description Neutrophils are first-responders to sites of infection and tissue damage including the inflamed tumor microenvironment. Increasing evidence suggests that crosstalk between tumors and neutrophils can affect the progression of established tumors. However, there is a gap in our understanding of the early events that lead to neutrophil recruitment to oncogene-transformed cells and how these pathways alter tumor progression. Here, we use optically transparent zebrafish larvae to probe the early signals that mediate neutrophil recruitment to Kras-transformed astrocytes. We show that zebrafish larvae with impaired neutrophil function exhibit reduced proliferation of transformed astrocytes supporting a critical role for tumor-associated neutrophils in the early progression of tumorigenesis. Moreover, using mutants and pharmacological inhibition, we show that the chemokine receptor Cxcr1 promotes neutrophil recruitment, proliferation of tumor-initiating cells, and neoplastic mass formation. These findings highlight the power of the larval zebrafish system to image and probe early events in the tumor-initiating microenvironment and demonstrate the potential for neutrophil recruitment signaling pathways such as Cxcl8-Cxcr1 as targets for anti-cancer therapies.
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spelling pubmed-61254802018-09-10 Cxcr1 mediates recruitment of neutrophils and supports proliferation of tumor-initiating astrocytes in vivo Powell, Davalyn Lou, Meng Barros Becker, Francisco Huttenlocher, Anna Sci Rep Article Neutrophils are first-responders to sites of infection and tissue damage including the inflamed tumor microenvironment. Increasing evidence suggests that crosstalk between tumors and neutrophils can affect the progression of established tumors. However, there is a gap in our understanding of the early events that lead to neutrophil recruitment to oncogene-transformed cells and how these pathways alter tumor progression. Here, we use optically transparent zebrafish larvae to probe the early signals that mediate neutrophil recruitment to Kras-transformed astrocytes. We show that zebrafish larvae with impaired neutrophil function exhibit reduced proliferation of transformed astrocytes supporting a critical role for tumor-associated neutrophils in the early progression of tumorigenesis. Moreover, using mutants and pharmacological inhibition, we show that the chemokine receptor Cxcr1 promotes neutrophil recruitment, proliferation of tumor-initiating cells, and neoplastic mass formation. These findings highlight the power of the larval zebrafish system to image and probe early events in the tumor-initiating microenvironment and demonstrate the potential for neutrophil recruitment signaling pathways such as Cxcl8-Cxcr1 as targets for anti-cancer therapies. Nature Publishing Group UK 2018-09-05 /pmc/articles/PMC6125480/ /pubmed/30185911 http://dx.doi.org/10.1038/s41598-018-31675-0 Text en © The Author(s) 2018 Open Access 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 http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Powell, Davalyn
Lou, Meng
Barros Becker, Francisco
Huttenlocher, Anna
Cxcr1 mediates recruitment of neutrophils and supports proliferation of tumor-initiating astrocytes in vivo
title Cxcr1 mediates recruitment of neutrophils and supports proliferation of tumor-initiating astrocytes in vivo
title_full Cxcr1 mediates recruitment of neutrophils and supports proliferation of tumor-initiating astrocytes in vivo
title_fullStr Cxcr1 mediates recruitment of neutrophils and supports proliferation of tumor-initiating astrocytes in vivo
title_full_unstemmed Cxcr1 mediates recruitment of neutrophils and supports proliferation of tumor-initiating astrocytes in vivo
title_short Cxcr1 mediates recruitment of neutrophils and supports proliferation of tumor-initiating astrocytes in vivo
title_sort cxcr1 mediates recruitment of neutrophils and supports proliferation of tumor-initiating astrocytes in vivo
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6125480/
https://www.ncbi.nlm.nih.gov/pubmed/30185911
http://dx.doi.org/10.1038/s41598-018-31675-0
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