Tumour extracellular vesicles and particles induce liver metabolic dysfunction.

1. Nature. 2023 Jun;618(7964):374-382. doi: 10.1038/s41586-023-06114-4. Epub 2023 May 24. Tumour extracellular vesicles and particles induce liver metabolic dysfunction. Wang G(#)(1), Li J(#)(1)(2), Bojmar L(1)(3), Chen H(1)(4)(5), Li Z(6), Tobias GC(1), Hu M(1), Homan EA(7), Lucotti S(1), Zhao F(1)(8), Posada V(9), Oxley PR(10), Cioffi M(1), Kim HS(1)(11), Wang H(1), Lauritzen P(1), Boudreau N(1), Shi Z(2), Burd CE(9), Zippin JH(12), Lo JC(7), Pitt GS(7), Hernandez J(13)(14), Zambirinis CP(13)(15), Hollingsworth MA(16), Grandgenett PM(16), Jain M(16), Batra SK(16), DiMaio DJ(17), Grem JL(18), Klute KA(18), Trippett TM(19), Egeblad M(20), Paul D(21), Bromberg J(22), Kelsen D(23), Rajasekhar VK(24), Healey JH(24), Matei IR(1), Jarnagin WR(13), Schwartz RE(25), Zhang H(26), Lyden D(27). Author information: (1)Children's Cancer and Blood Foundation Laboratories, Departments of Pediatrics, and Cell and Developmental Biology, Drukier Institute for Children's Health, Meyer Cancer Center, Weill Cornell Medicine, New York, NY, USA. (2)Department of Orthopedic Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, China. (3)Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden. (4)Department of Radiation Oncology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China. (5)Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, Key Laboratory of Molecular Biology in Medical Sciences, Hangzhou, China. (6)Duke Proteomics and Metabolomics Shared Resource, Duke University School of Medicine, Durham, NC, USA. (7)Cardiovascular Research Institute and Department of Medicine, Weill Cornell Medicine, New York, NY, USA. (8)Basic Medical Research Center, Medical School of Nantong University, Nantong, China. (9)Departments of Molecular Genetics, Cancer Biology and Genetics, The Ohio State University, Columbus, OH, USA. (10)Samuel J. Wood Library, Weill Cornell Medicine, New York, NY, USA. (11)Yonsei Cancer Center, Division of Medical Oncology, Department of Internal Medicine, Brain Korea 21 FOUR Project for Medical Science, Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul, Korea. (12)Department of Dermatology, Weill Cornell Medical College of Cornell University, New York, NY, USA. (13)Hepatopancreatobiliary Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA. (14)Thoracic and Gastrointestinal Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA. (15)Division of Surgical Oncology, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, USA. (16)Fred and Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE, USA. (17)Department of Pathology and Microbiology, College of Medicine, University of Nebraska Medical Center, Omaha, NE, USA. (18)Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE, USA. (19)Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, NY, USA. (20)Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, USA. (21)Division of Hematology and Medical Oncology, Department of Medicine, Weill Cornell Medicine, New York, NY, USA. (22)Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA. (23)Gastrointestinal Oncology Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA. (24)Orthopedic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA. (25)Division of Gastroenterology and Hepatology, Department of Medicine, Weill Cornell Medicine, New York, NY, USA. res2025@med.cornell.edu. (26)Children's Cancer and Blood Foundation Laboratories, Departments of Pediatrics, and Cell and Developmental Biology, Drukier Institute for Children's Health, Meyer Cancer Center, Weill Cornell Medicine, New York, NY, USA. haz2005@med.cornell.edu. (27)Children's Cancer and Blood Foundation Laboratories, Departments of Pediatrics, and Cell and Developmental Biology, Drukier Institute for Children's Health, Meyer Cancer Center, Weill Cornell Medicine, New York, NY, USA. dcl2001@med.cornell.edu. (#)Contributed equally Comment in Nat Rev Cancer. 2023 Aug;23(8):510. doi: 10.1038/s41568-023-00597-z. Cancer alters the function of multiple organs beyond those targeted by metastasis1,2. 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 palmit