“A distinct neutrophil population invades the central nervous system during pancreatic cancer”
“A distinct neutrophil population invades the central nervous system during pancreatic cancer”
Abstract Weight loss, fatigue, and cognitive dysfunction 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. CCR2 knockout mice had significantly decreased brain-infiltrating neutrophils as well as attenuated anorexia and muscle catabolism during PDAC, without any changes in neutrophils in other organs. Lastly, intracerebroventricular blockade of the purinergic receptor P2RX7 during PDAC abolished neutrophil 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.
Olson Brennan、Torres Eileen Ruth S.、Jeng Sophia、Raber Jacob、Marks Daniel L.、Zhu Xinxia、Patel Esha M.、Levasseur Peter R.、McWeeney Shannon、Norgard Mason A.、Michaelis Katherine A.、Burfeind Kevin G.
Pap¨| Family Pediatric Research Institute, Oregon Health & Science University||Medical Scientist Training Program, Oregon Health & Science UniversityDepartment of Behavioral Neuroscience, Oregon Health & Science UniversityOregon Clinical and Translational Research Institute, Oregon Health & Science University||Knight Cancer Institute, Oregon Health & Science UniversityDepartment of Behavioral Neuroscience, Oregon Health & Science University||Departments of Neurology and Radiation Medicine, Division of Neuroscience ONPRC, Oregon Health and & Science UniversityPap¨| Family Pediatric Research Institute, Oregon Health & Science University||Knight Cancer Institute, Oregon Health & Science University||Brenden-Colson Center for Pancreatic Care, Oregon Health and & Science UniversityPap¨| Family Pediatric Research Institute, Oregon Health & Science UniversityDepartment of Behavioral Neuroscience, Oregon Health & Science UniversityPap¨| Family Pediatric Research Institute, Oregon Health & Science UniversityDivision of Bioinformatics and Computational Biology, Department of Medical Informatics and Clinical Epidemiology, Oregon Health & Science University||Oregon Clinical and Translational Research Institute, Oregon Health & Science University||Knight Cancer Institute, Oregon Health & Science UniversityPap¨| Family Pediatric Research Institute, Oregon Health & Science UniversityPap¨| Family Pediatric Research Institute, Oregon Health & Science University||Medical Scientist Training Program, Oregon Health & Science UniversityPap¨| Family Pediatric Research Institute, Oregon Health & Science University||Medical Scientist Training Program, Oregon Health & Science University
肿瘤学神经病学、精神病学基础医学
NeuroinflammationNeuroimmunologyNeutrophilsCancer CachexiaBrainMyeloid Cells
Olson Brennan,Torres Eileen Ruth S.,Jeng Sophia,Raber Jacob,Marks Daniel L.,Zhu Xinxia,Patel Esha M.,Levasseur Peter R.,McWeeney Shannon,Norgard Mason A.,Michaelis Katherine A.,Burfeind Kevin G..“A distinct neutrophil population invades the central nervous system during pancreatic cancer”[EB/OL].(2025-03-28)[2025-05-15].https://www.biorxiv.org/content/10.1101/659060.点此复制
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