ROS-Induced CXCR4 Signaling Regulates Mantle Cell Lymphoma (MCL) Cell Survival and Drug Resistance in the Bone Marrow Microenvironment via Autophagy

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
Zheng ChenN McCarty

Abstract

Patients with advanced stages of mantle cell lymphoma (MCL) have a poor prognosis after standard therapies. MCL cells in those patients often spread into tissues other than lymph nodes, such as the bone marrow. Apart from directed migration and homing, there is little understanding of the function of the CXCR4/SDF-1 signaling axis in MCL. In this report, we aim to understand mechanisms of MCL cell survival in the bone marrow. For comprehensive analyses of MCL interactions with bone marrow stromal cells, we have generated gene knockout cells using CRISPR-CAS9 system and gene knockdown cells to reveal novel roles of the CXCR4/SDF-1 signaling. CXCR4 silencing in MCL cells led to a significant reduction in proliferation, cell adhesion to bone marrow stromal cells, and colony formation in PHA-LCM methylcellulose medium, which were reversed upon the addition of SDF-1-neutralizing antibodies. In addition, tracking MCL cell engraftment in vivo revealed that quiescent MCL cells are significantly reduced in the bone marrow upon CXCR4 silencing, indicating that CXCR4/SDF-1 signaling is required for the survival and maintenance of the quiescent MCL cells. Further analysis revealed novel mechanisms of ROS-induced CXCR4/SDF-1 signaling that ...Continue Reading

References

Dec 6, 2000·The Journal of Clinical Investigation·T PonomaryovT Lapidot
Nov 25, 2003·Blood·William MatsuiRichard J Jones
Jun 1, 2005·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Giovanni GrignaniMassimo Aglietta
Aug 27, 2005·Blood·Kai FuUNKNOWN Lymphoma/Leukemia Molecular Profiling Project
Apr 13, 2007·Nature·Beth Levine
Jan 15, 2008·Cell·Beth Levine, Guido Kroemer
Dec 17, 2008·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Peter MartinJohn P Leonard
Sep 1, 2009·Clinical Lymphoma & Myeloma·John P LeonardJohn W Sweetenham
Oct 30, 2009·Leukemia & Lymphoma·Oliver WeigertMartin Dreyling
Nov 20, 2009·Cancer Biology & Therapy·Anália do CarmoMaria C Lopes
Feb 12, 2010·Cancer Biology & Therapy·Tara GangadharRavi Salgia
Dec 4, 2010·Science·Joshua D Rabinowitz, Eileen White
Apr 21, 2011·Expert Review of Anticancer Therapy·Jan A BurgerAmnon Peled
May 19, 2011·Breast Cancer Research : BCR·Philippe Clézardin
May 19, 2011·British Journal of Cancer·D TsengJ M Brown
Jun 3, 2011·Journal of Neuro-oncology·Sachiko Ohshima-HosoyamaCharles Keller
Jan 21, 2012·The Journal of Pathology·Vanessa RauschIngrid Herr
Jul 24, 2012·Free Radical Biology & Medicine·Lin LiSpencer B Gibson
Aug 11, 2012·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Laia RosichGaël Roué
Nov 28, 2012·Frontiers in Oncology·Sameera Kongara, Vassiliki Karantza
Feb 8, 2013·Nature·Matthew R WarrEmmanuelle Passegué

❮ Previous
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Citations

May 27, 2016·The Plant Journal : for Cell and Molecular Biology·Justine Braguy, Matias D Zurbriggen
Sep 14, 2016·British Journal of Haematology·Han Zhang, Nami McCarty
Sep 7, 2016·Expert Opinion on Drug Discovery·Federica BarbieriTullio Florio
Jan 31, 2018·International Journal of Hematology·Han Zhang
Feb 2, 2019·Cells·Mojgan Djavaheri-MergnyMagali Humbert
Mar 9, 2019·Current Hematologic Malignancy Reports·Jordan N Noble, Anjali Mishra
Apr 19, 2017·Oncotarget·Marta IrigoyenEdurne Berra
Feb 6, 2020·International Journal of Molecular Sciences·Anuvrat SircarNarendranath Epperla
Aug 21, 2019·Frontiers in Endocrinology·Lan Xiao, Yin Xiao
Mar 22, 2020·International Journal of Molecular Sciences·Pavel Klener, Magdalena Klanova
Aug 28, 2020·Expert Opinion on Therapeutic Targets·Pavel Klener
Mar 30, 2017·Cancer Immunology Research·Xuyao ZhangDianwen Ju
Apr 5, 2017·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
Jul 2, 2019·Journal of Molecular Biology·Sebastian E Koschade, Christian H Brandts
May 20, 2018·Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine·Constantin LapaGötz Ulrich Grigoleit
Aug 28, 2021·International Journal of Molecular Sciences·Ioanna E Stergiou, Efstathia K Kapsogeorgou

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