The CXCR4 antagonist plerixafor (AMD3100) promotes proliferation of Ewing sarcoma cell lines in vitro and activates receptor tyrosine kinase signaling.

Cell Communication and Signaling : CCS
Philipp BerningJenny Potratz

Abstract

The CXCR4 receptor antagonist plerixafor (AMD3100) is raising interest as an anti-cancer agent that disrupts the CXCL12-CXCR4 chemokine - receptor interaction between neoplastic cells and their microenvironment in tumor progression and metastasis. Here, we investigated plerixafor for anti-cancer activity in Ewing sarcoma, a rare and aggressive cancer of bone and soft tissues. We used a variety of methods such as cell viability and migration assays, flow cytometry, phospho-tyrosine arrays and western blotting to determine plerixafor effects on five characterized Ewing sarcoma cell lines and a low-passage culture in vitro. Unexpectedly, plerixafor led to an increase in cell viability and proliferation in standard cell growth conditions, and to chemotactic migration towards plerixafor. Exploring potential molecular mechanisms underlying this effect, we found that Ewing sarcoma cell lines divided into classes of high- and low-level CXCR4 surface expression. Proliferative plerixafor responses were observed in both groups, maintained despite significant CXCR4 down-regulation or inhibition of Gαi-protein signal transduction, and involved activation of multiple receptor tyrosine kinases (DDR2, MERTK, MST1R, NTRK1, RET), the most promin...Continue Reading

References

Sep 11, 2002·FEBS Letters·Sigrid HatseDominique Schols
Mar 11, 2003·American Journal of Respiratory and Critical Care Medicine·Roderick J PhillipsRobert M Strieter
Jul 2, 2004·Nature Reviews. Cancer·Fran Balkwill
Nov 16, 2004·Cancer Cell·Yan M LiMien-Chie Hung
Mar 8, 2005·Immunology and Cell Biology·Andrew J SloaneGarry W Lynch
Apr 20, 2005·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Joseph KimDave S B Hoon
Jan 7, 2006·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Irma AiroldiVito Pistoia
Aug 31, 2006·The Journal of Experimental Medicine·Jennifer M BurnsThomas J Schall
Oct 5, 2007·Pediatric Blood & Cancer·E Anders KolbMalcolm A Smith
Dec 18, 2008·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Donald Wong, Walter Korz
Jan 13, 2009·Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation·Douglas A StewartGary Calandra
Mar 4, 2009·Molecular Pharmacology·Irina KalatskayaNikolaus Heveker
Oct 20, 2009·European Journal of Pharmacology·Radoslaw B MaksymMariusz Z Ratajczak
Feb 18, 2010·International Journal of Cancer. Journal International Du Cancer·Katarzyna GrymulaMariusz Z Ratajczak
Jun 8, 2010·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Idriss M Bennani-BaitiHeinrich Kovar
Jun 16, 2010·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Ruth LadensteinHeribert Jürgens
Jan 22, 2011·Cancer Research and Treatment : Official Journal of Korean Cancer Association·Ha-Yon KimDeog-Yeon Jo
Feb 26, 2011·Journal of Translational Medicine·Claudia RubieMartin K Schilling
Jul 12, 2011·The FEBS Journal·Camille LochtNathalie Mielcarek
Sep 14, 2011·Molecular Cancer Research : MCR·Randala HamdanEugenie S Kleinerman
Jun 12, 2012·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·Urszula M DomanskaAnnemiek M E Walenkamp
Dec 20, 2012·Clinical Sarcoma Research·Dagmar BerghuisArjan C Lankester
Mar 19, 2014·Molecular Cancer·Benoît RomainDominique Guenot
Mar 22, 2014·Molecular Cancer Research : MCR·Melanie A KrookElizabeth R Lawlor
Apr 24, 2014·Recent Results in Cancer Research. Fortschritte Der Krebsforschung. Progrès Dans Les Recherches Sur Le Cancer·Markus Lindauer, Andreas Hochhaus
Aug 26, 2015·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Nathalie GasparOdile Oberlin
Sep 1, 2015·Biochemical and Biophysical Research Communications·L G L SandK Szuhai
Oct 3, 2015·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·L G L SandP C W Hogendoorn
Nov 5, 2016·Molecular Cancer·M Katie Conley-LaCombSreenivasa R Chinni

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Citations

Jul 2, 2019·International Journal of Molecular Medicine·Yingzheng WengLijiang Tang
Apr 25, 2019·JCO Precision Oncology·Roberto Carmagnani PestanaVivek Subbiah
Dec 10, 2020·Journal for Immunotherapy of Cancer·Erin MoralesDjordje Atanackovic
Feb 14, 2021·European Journal of Pharmacology·Simona DanieleLuciana Marinelli
Jan 5, 2021·Frontiers in Oncology·Guang-Quan LiangHenry Wei
Nov 5, 2020·Cell Reports·Fuchun ZhouYuzuru Shiio

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Methods Mentioned

BETA
environmental stresses
FACS
PCR
flow cytometry
glycosylation
ubiquitination

Software Mentioned

MRI Wound Healing Tool
Image J
FACS
GraphPad Prism
FlowJo
Excel

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