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Tumour extracellula...
Tumour extracellular vesicles and particles induce liver metabolic dysfunction
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- Wang, Gang (author)
- Weill Cornell Med, NY 10021 USA; Weill Cornell Med, NY 10021 USA
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- Li, Jianlong (author)
- Weill Cornell Med, NY 10021 USA; Weill Cornell Med, NY 10021 USA; Southern Med Univ, Peoples R China
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- Bojmar, Linda, 1983- (author)
- Linköpings universitet,Avdelningen för kirurgi, ortopedi och onkologi,Medicinska fakulteten,Weill Cornell Med, NY 10021 USA; Weill Cornell Med, NY 10021 USA
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- Chen, Haiyan (author)
- Weill Cornell Med, NY 10021 USA; Weill Cornell Med, NY 10021 USA; Zhejiang Univ, Peoples R China; China Natl Minist Educ, Peoples R China
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- Li, Zhong (author)
- Duke Univ, NC USA
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- Tobias, Gabriel C. (author)
- Weill Cornell Med, NY 10021 USA; Weill Cornell Med, NY 10021 USA
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- Hu, Mengying (author)
- Weill Cornell Med, NY 10021 USA; Weill Cornell Med, NY 10021 USA
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- Homan, Edwin A. (author)
- Weill Cornell Med, NY USA; Weill Cornell Med, NY USA
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- Lucotti, Serena (author)
- Weill Cornell Med, NY 10021 USA; Weill Cornell Med, NY 10021 USA
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- Zhao, Fengbo (author)
- Weill Cornell Med, NY 10021 USA; Weill Cornell Med, NY 10021 USA; Nantong Univ, Peoples R China
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- Posada, Valentina (author)
- Ohio State Univ, OH USA; Ohio State Univ, OH USA
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- Oxley, Peter R. (author)
- Weill Cornell Med, NY USA
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- Cioffi, Michele (author)
- Weill Cornell Med, NY 10021 USA; Weill Cornell Med, NY 10021 USA
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- Kim, Han Sang (author)
- Weill Cornell Med, NY 10021 USA; Weill Cornell Med, NY 10021 USA; Yonsei Univ, South Korea
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- Wang, Huajuan (author)
- Weill Cornell Med, NY 10021 USA; Weill Cornell Med, NY 10021 USA
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- Lauritzen, Pernille (author)
- Weill Cornell Med, NY 10021 USA; Weill Cornell Med, NY 10021 USA
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- Boudreau, Nancy (author)
- Weill Cornell Med, NY 10021 USA; Weill Cornell Med, NY 10021 USA
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- Shi, Zhanjun (author)
- Southern Med Univ, Peoples R China
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- Burd, Christin E. (author)
- Ohio State Univ, OH USA; Ohio State Univ, OH USA
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- Zippin, Jonathan H. (author)
- Cornell Univ, NY USA
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- Lo, James C. (author)
- Weill Cornell Med, NY USA; Weill Cornell Med, NY USA
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- Pitt, Geoffrey S. (author)
- Weill Cornell Med, NY USA; Weill Cornell Med, NY USA
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- Hernandez, Jonathan (author)
- Mem Sloan Kettering Canc Ctr, NY USA; NCI, MD USA
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- Zambirinis, Constantinos P. (author)
- Mem Sloan Kettering Canc Ctr, NY USA; Rutgers Canc Inst New Jersey, NJ USA
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- Hollingsworth, Michael A. (author)
- Univ Nebraska Med Ctr, NE USA
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- Grandgenett, Paul M. (author)
- Univ Nebraska Med Ctr, NE USA
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- Jain, Maneesh (author)
- Univ Nebraska Med Ctr, NE USA
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- Batra, Surinder K. (author)
- Univ Nebraska Med Ctr, NE USA
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- DiMaio, Dominick J. (author)
- Univ Nebraska Med Ctr, NE USA
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- Grem, Jean L. (author)
- Univ Nebraska Med Ctr, NE USA
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- Klute, Kelsey A. (author)
- Univ Nebraska Med Ctr, NE USA
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- Trippett, Tanya M. (author)
- Mem Sloan Kettering Canc Ctr, NY USA
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- Egeblad, Mikala (author)
- Cold Spring Harbor Lab, NY USA
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- Paul, Doru (author)
- Weill Cornell Med, NY USA
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- Bromberg, Jacqueline (author)
- Mem Sloan Kettering Canc Ctr, NY USA
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- Kelsen, David (author)
- Mem Sloan Kettering Canc Ctr, NY USA
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- Rajasekhar, Vinagolu K. (author)
- Mem Sloan Kettering Canc Ctr, NY USA
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- Healey, John H. (author)
- Mem Sloan Kettering Canc Ctr, NY USA
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- Matei, Irina R. (author)
- Weill Cornell Med, NY 10021 USA; Weill Cornell Med, NY 10021 USA
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- Jarnagin, William R. (author)
- Hepatopancreatobiliary Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
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- Schwartz, Robert E. (author)
- Division of Gastroenterology and Hepatology, Department of Medicine, Weill Cornell Medicine, New York, NY, USA
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- Zhang, Haiying (author)
- Weill Cornell Med, NY 10021 USA; Weill Cornell Med, NY 10021 USA
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- Lyden, David (author)
- Weill Cornell Med, NY 10021 USA; Weill Cornell Med, NY 10021 USA
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(creator_code:org_t)
- NATURE PORTFOLIO, 2023
- 2023
- English.
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In: Nature. - : NATURE PORTFOLIO. - 0028-0836 .- 1476-4687. ; 618:7964, s. 374-382
- Related links:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Subject headings
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- Cancer alters the function of multiple organs beyond those targeted by metastasis(1,2). Here we show that inflammation, fatty liver and dysregulated metabolism are hallmarks of systemically affected livers in mouse models and in patients with extrahepatic metastasis. We identified tumour-derived extracellular vesicles and particles (EVPs) as crucial mediators of cancer-induced hepatic reprogramming, which could be reversed by reducing tumour EVP secretion via depletion of Rab27a. All EVP subpopulations, exosomes and principally exomeres, could dysregulate hepatic function. The fatty acid cargo of tumour EVPs-particularly palmitic acid-induced secretion of tumour necrosis factor (TNF) by Kupffer cells, generating a pro-inflammatory microenvironment, suppressing fatty acid metabolism and oxidative phosphorylation, and promoting fatty liver formation. Notably, Kupffer cell ablation or TNF blockade markedly decreased tumour-induced fatty liver generation. Tumour implantation or pre-treatment with tumour EVPs diminished cytochrome P450 gene expression and attenuated drug metabolism in a TNF-dependent manner. We also observed fatty liver and decreased cytochrome P450 expression at diagnosis in tumour-free livers of patients with pancreatic cancer who later developed extrahepatic metastasis, highlighting the clinical relevance of our findings. Notably, tumour EVP education enhanced side effects of chemotherapy, including bone marrow suppression and cardiotoxicity, suggesting that metabolic reprogramming of the liver by tumour-derived EVPs may limit chemotherapy tolerance in patients with cancer. Our results reveal how tumour-derived EVPs dysregulate hepatic function and their targetable potential, alongside TNF inhibition, for preventing fatty liver formation and enhancing the efficacy of chemotherapy.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
Publication and Content Type
- ref (subject category)
- art (subject category)
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Nature
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To the university's database
- By the author/editor
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Wang, Gang
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Li, Jianlong
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Bojmar, Linda, 1 ...
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Chen, Haiyan
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Li, Zhong
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Tobias, Gabriel ...
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show more...
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Hu, Mengying
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Homan, Edwin A.
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Lucotti, Serena
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Zhao, Fengbo
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Posada, Valentin ...
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Oxley, Peter R.
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Cioffi, Michele
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Kim, Han Sang
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Wang, Huajuan
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Lauritzen, Perni ...
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Boudreau, Nancy
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Shi, Zhanjun
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Burd, Christin E ...
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Zippin, Jonathan ...
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Lo, James C.
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Pitt, Geoffrey S ...
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Hernandez, Jonat ...
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Zambirinis, Cons ...
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Hollingsworth, M ...
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Grandgenett, Pau ...
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Jain, Maneesh
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Batra, Surinder ...
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DiMaio, Dominick ...
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Grem, Jean L.
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Klute, Kelsey A.
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Trippett, Tanya ...
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Egeblad, Mikala
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Paul, Doru
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Bromberg, Jacque ...
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Kelsen, David
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Rajasekhar, Vina ...
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Healey, John H.
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Matei, Irina R.
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Jarnagin, Willia ...
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Schwartz, Robert ...
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Zhang, Haiying
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Lyden, David
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Cell and Molecul ...
- Articles in the publication
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Nature
- By the university
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Linköping University