Abstract
Human lung squamous cell carcinoma (SCC) is highly associated with increased pulmonary macrophage infiltration. Previously, we showed that marked pulmonary infiltrating macrophages were required for spontaneous lung SCC development in a mouse model (L-Ikkα
KA/KA
, KA/KA) that resembles human lung SCC. Interestingly the lung SCC-associated macrophages specifically express elevated inducible nitric oxide synthase (NOS2). However, the role of macrophage NOS2 in lung carcinogenesis has not been explored. Here, we show that NOS2 ablation inhibits macrophage infiltration, fibrosis, and SCC development in the lungs of KA/KA mice. Macrophage NOS2 was found to circulate inflammation and enhance macrophage migration and survival. NOS2 promotes foamy macrophage formation characterized with impaired lipid metabolism. NOS2 null bone marrow transplantation reduces foamy macrophage numbers and carcinogenesis in KA/KA chimaeras. This finding sheds light on a new mechanism by which macrophage NOS2 increases pulmonary inflammatory responses and macrophage survival and impairs macrophage lipid metabolism, thereby promoting lung SCC formation.
References
Oct 10, 1986·Cell·Y C YangG G Wong
Aug 26, 1998·British Journal of Cancer·C Y LiuH P Kuo
Jul 8, 2005·Journal of Leukocyte Biology·Nancy J PoindexterElizabeth A Grimm
Nov 3, 2006·Proceedings of the National Academy of Sciences of the United States of America·Bigang LiuYinling Hu
Oct 26, 2007·Clinical Reviews in Allergy & Immunology·David NicholsMelvin Berger
Sep 6, 2008·Cancer Cell·Bigang LiuYinling Hu
Sep 26, 2008·The New England Journal of Medicine·Roy S HerbstScott M Lippman
Apr 8, 2010·Annual Review of Biochemistry·Brian R CraneBhumit A Patel
Jul 9, 2010·CA: a Cancer Journal for Clinicians·Ahmedin JemalElizabeth Ward
May 1, 2012·Blood·Mumtaz Yaseen BalkhiYinling Hu
May 24, 2012·International Journal of Cancer. Journal International Du Cancer·Hirokazu OkayamaCurtis C Harris
Feb 5, 2013·The Journal of Clinical Investigation·Anthony RousselleJohan Duchene
Mar 12, 2013·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·Hayet RafaChafia Touil-Boukoffa
Mar 29, 2013·PloS One·Manoj K BarthwalHoward S Kruth
Apr 20, 2013·Cancer Cell·Zuoxiang XiaoYinling Hu
May 6, 2014·Cancer Cell·Chunxiao XuKwok-Kin Wong
Oct 1, 2014·Nature Communications·Bradley N MartinXiaoxia Li
Oct 28, 2014·Frontiers in Immunology·Joshua T Mattila, Anita C Thomas
Nov 12, 2014·Frontiers in Immunology·Meera RathMarkus Munder
Jun 20, 2015·Mediators of Inflammation·Tamás Rőszer
Jun 27, 2015·The European Respiratory Journal·Mathieu C MorissetteMartin R Stämpfli
Aug 12, 2015·British Journal of Cancer·Wenqing CaoJiangZhou Yu
Feb 3, 2016·Current Opinion in Lipidology·Joshua A Dubland, Gordon A Francis
Feb 11, 2016·Oncotarget·Eyra MarienJohannes V Swinnen
Nov 1, 2016·Antioxidants & Redox Signaling·Graciele Almeida de OliveiraDavid A Wink
Citations
Jan 27, 2019·The Journal of Pathology·Simon MiletteDaniela F Quail
Dec 11, 2019·Diagnostics·Antonia HarangușMărioara Șimon
Oct 2, 2020·Journal of Receptor and Signal Transduction Research·Bo ZhangGuoping Chen
May 31, 2018·Cell Death & Disease·Zane GrayYinling Hu
Sep 19, 2019·Evidence-based Complementary and Alternative Medicine : ECAM·Yan HuangXueping Zhou
Jul 25, 2020·Journal of Applied Microbiology·A R BalasubramanianP Neelakantan
Nov 11, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Mariusz G FleszarMałgorzata Krzystek-Korpacka
Aug 24, 2020·European Journal of Pharmacology·Daryoush Hamidi AlamdariGeorge Koliakos
Jan 16, 2020·Immunity·Jérôme Galon, Daniela Bruni
Jan 8, 2021·Cell and Tissue Research·Denusha ShresthaChandrashekhar Charavaryamath
Apr 4, 2021·Cancers·Xin Li, Yinling Hu