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Circulating myeloid cells invade the central nervous system to mediate cachexia during pancreatic cancer
Weight loss and anorexia are common symptoms in cancer patients that occur prior to initiation of cancer therapy. Inflammation in the brain is a driver of these symptoms, yet cellular sources of neuroinflammation during malignancy are unknown. In a mouse model of pancreatic ductal adenocarcinoma (PD...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
eLife Sciences Publications, Ltd
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7253193/ https://www.ncbi.nlm.nih.gov/pubmed/32391790 http://dx.doi.org/10.7554/eLife.54095 |
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author | Burfeind, Kevin G Zhu, Xinxia Norgard, Mason A Levasseur, Peter R Huisman, Christian Buenafe, Abigail C Olson, Brennan Michaelis, Katherine A Torres, Eileen RS Jeng, Sophia McWeeney, Shannon Raber, Jacob Marks, Daniel L |
author_facet | Burfeind, Kevin G Zhu, Xinxia Norgard, Mason A Levasseur, Peter R Huisman, Christian Buenafe, Abigail C Olson, Brennan Michaelis, Katherine A Torres, Eileen RS Jeng, Sophia McWeeney, Shannon Raber, Jacob Marks, Daniel L |
author_sort | Burfeind, Kevin G |
collection | PubMed |
description | Weight loss and anorexia are common symptoms in cancer patients that occur prior to initiation of cancer therapy. Inflammation in the brain is a driver of these symptoms, yet cellular sources of neuroinflammation during malignancy are unknown. In a mouse model of pancreatic ductal adenocarcinoma (PDAC), we observed early and robust myeloid cell infiltration into the brain. Infiltrating immune cells were predominately neutrophils, which accumulated at a unique central nervous system entry portal called the velum interpositum, where they expressed CCR2. Pharmacologic CCR2 blockade and genetic deletion of Ccr2 both resulted in significantly decreased brain-infiltrating myeloid cells as well as attenuated cachexia during PDAC. Lastly, intracerebroventricular blockade of the purinergic receptor P2RX7 during PDAC abolished immune cell recruitment to the brain and attenuated anorexia. Our data demonstrate a novel function for the CCR2/CCL2 axis in recruiting neutrophils to the brain, which drives anorexia and muscle catabolism. |
format | Online Article Text |
id | pubmed-7253193 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-72531932020-06-02 Circulating myeloid cells invade the central nervous system to mediate cachexia during pancreatic cancer Burfeind, Kevin G Zhu, Xinxia Norgard, Mason A Levasseur, Peter R Huisman, Christian Buenafe, Abigail C Olson, Brennan Michaelis, Katherine A Torres, Eileen RS Jeng, Sophia McWeeney, Shannon Raber, Jacob Marks, Daniel L eLife Immunology and Inflammation Weight loss and anorexia are common symptoms in cancer patients that occur prior to initiation of cancer therapy. Inflammation in the brain is a driver of these symptoms, yet cellular sources of neuroinflammation during malignancy are unknown. In a mouse model of pancreatic ductal adenocarcinoma (PDAC), we observed early and robust myeloid cell infiltration into the brain. Infiltrating immune cells were predominately neutrophils, which accumulated at a unique central nervous system entry portal called the velum interpositum, where they expressed CCR2. Pharmacologic CCR2 blockade and genetic deletion of Ccr2 both resulted in significantly decreased brain-infiltrating myeloid cells as well as attenuated cachexia during PDAC. Lastly, intracerebroventricular blockade of the purinergic receptor P2RX7 during PDAC abolished immune cell recruitment to the brain and attenuated anorexia. Our data demonstrate a novel function for the CCR2/CCL2 axis in recruiting neutrophils to the brain, which drives anorexia and muscle catabolism. eLife Sciences Publications, Ltd 2020-05-11 /pmc/articles/PMC7253193/ /pubmed/32391790 http://dx.doi.org/10.7554/eLife.54095 Text en © 2020, Burfeind et al http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited. |
spellingShingle | Immunology and Inflammation Burfeind, Kevin G Zhu, Xinxia Norgard, Mason A Levasseur, Peter R Huisman, Christian Buenafe, Abigail C Olson, Brennan Michaelis, Katherine A Torres, Eileen RS Jeng, Sophia McWeeney, Shannon Raber, Jacob Marks, Daniel L Circulating myeloid cells invade the central nervous system to mediate cachexia during pancreatic cancer |
title | Circulating myeloid cells invade the central nervous system to mediate cachexia during pancreatic cancer |
title_full | Circulating myeloid cells invade the central nervous system to mediate cachexia during pancreatic cancer |
title_fullStr | Circulating myeloid cells invade the central nervous system to mediate cachexia during pancreatic cancer |
title_full_unstemmed | Circulating myeloid cells invade the central nervous system to mediate cachexia during pancreatic cancer |
title_short | Circulating myeloid cells invade the central nervous system to mediate cachexia during pancreatic cancer |
title_sort | circulating myeloid cells invade the central nervous system to mediate cachexia during pancreatic cancer |
topic | Immunology and Inflammation |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7253193/ https://www.ncbi.nlm.nih.gov/pubmed/32391790 http://dx.doi.org/10.7554/eLife.54095 |
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