CXCL12; cancer stem cells; invasion; stem cell microenvironment
Abstract :
[en] BACKGROUND: Patients with glioblastoma multiforme (GBM) have an overall median survival of 15 months. This catastrophic survival rate is the consequence of systematic relapses that could arise from remaining glioblastoma stem cells (GSCs) left behind after surgery. We previously demonstrated that GSCs are able to escape the tumor mass and specifically colonize the adult subventricular zones (SVZs) after transplantation. This specific localization, away from the initial injection site, therefore represents a high-quality model of a clinical obstacle to therapy and relapses because GSCs notably retain the ability to form secondary tumors. METHOD: In this work, we questioned the role of the CXCL12/CXCR4 signaling in the GSC-specific invasion of the SVZs. RESULTS: We demonstrated that both receptor and ligand are respectively expressed by different GBM cell populations and by the SVZ itself. In vitro migration bio-assays highlighted that human U87MG GSCs isolated from the SVZs (U87MG-SVZ) display stronger migratory abilities in response to recombinant CXCL12 and/or SVZ-conditioned medium (SVZ-CM) compared with cancer cells isolated from the tumor mass (U87MG-TM). Moreover, in vitro inhibition of the CXCR4 signaling significantly decreased the U87MG-SVZ cell migration in response to the SVZ-CM. Very interestingly, treating U87MG-xenografted mice with daily doses of AMD3100, a specific CXCR4 antagonist, prevented the specific invasion of the SVZ. Another in vivo experiment, using CXCR4-invalidated GBM cells, displayed similar results. CONCLUSION: Taken together, these data demonstrate the significant role of the CXCL12/CXCR4 signaling in this original model of brain cancer invasion.
Disciplines :
Neurology Oncology Genetics & genetic processes
Author, co-author :
Goffart, Nicolas ; Université de Liège > Département des sciences biomédicales et précliniques > Biochimie et physiologie générales, et biochimie humaine
KROONEN, Jérôme ; Centre Hospitalier Universitaire de Liège - CHU > Centre d'oncologie
Di Valentin, Emmanuel ; Université de Liège - ULiège > Département des sciences de la vie > GIGA-R : Virologie et immunologie
Denne, Alexandre ; Université de Liège - ULiège > Master méd. (ex 4e master en 4 ans)
Martinive, Philippe ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Département des sciences biomédicales et précliniques
Rogister, Bernard ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Biochimie et physiologie générales, et biochimie humaine
Language :
English
Title :
Adult mouse subventricular zones stimulate glioblastoma stem cells specific invasion through CXCL12/CXCR4 signaling.
Publication date :
2015
Journal title :
Neuro-Oncology
ISSN :
1522-8517
eISSN :
1523-5866
Publisher :
Oxford University Press
Volume :
17
Issue :
1
Pages :
81-94
Peer reviewed :
Peer Reviewed verified by ORBi
Commentary :
(c) The Author(s) 2014. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
Louis DN, Ohgaki H, Wiestler OD, et al. The 2007 WHO classification of tumours of the central nervous system. Acta Neuropathol. 2007;114(2):97-109.
Furnari FB, Fenton T, Bachoo RM, et al. Malignant astrocytic glioma: genetics, biology, and paths to treatment. Genes Dev. 2007; 21(21):2683-2710.
Kroonen J, Nassen J, Boulanger YG, et al. Human glioblastoma-initiating cells invade specifically the subventricular zones and olfactory bulbs of mice after striatal injection. Int J Cancer. 2011;129(3):574-585.
Sadahiro H, Yoshikawa K, Ideguchi M, et al. Pathological features of highly invasive glioma stem cells in a mouse xenograft model. Brain Tumor Pathol. 2013;30(2):1-8.
Scadden DT. The stem-cell niche as an entity of action. Nature. 2006;441(7097):1075-1079.
Shen Q, Goderie SK, Jin L, et al. Endothelial cells stimulate self-renewal and expand neurogenesis of neural stem cells. Science. 2004;304(5675):1338-1340.
Calabrese C, Poppleton H, Kocak M, et al. A perivascular niche for brain tumor stem cells. Cancer Cell. 2007;11(11):69-82.
Folkins C, Man S, Xu P, et al. Anticancer therapies combining antiangiogenic and tumor cell cytotoxic effects reduce the tumor stem-like cell fraction in glioma xenograft tumors. Cancer Res. 2007;67(8):3560-3564.
Rempel SA, Dudas S, Ge S, et al. Identification and localization of the cytokine SDF1 and its receptor, CXC chemokine receptor 4, to regions of necrosis and angiogenesis in human glioblastoma. Clin Cancer Res. 2000;6(1):102-111.
Ehtesham M, Winston JA, Kabos P, et al. CXCR4 expression mediates glioma cell invasiveness. Oncogene. 2006;25(19): 2801-2806.
Rubin JB, Kung AL, Klein RS, et al. A small-molecule antagonist of CXCR4 inhibits intracranial growth of primary brain tumors. Proc Natl Acad Sci USA. 2003;100(23):13513-13518.
Bian XW, Yang SX, Chen JH, et al. Preferential expression of chemokine receptor CXCR4 by highly malignant human gliomas and its association with poor patient survival. Neurosurgery. 2007;61(3):570-578; discussion 578-579.
Oh JW, Drabik K, Kutsch O, et al. CXC chemokine receptor 4 expression and function in human astroglioma cells. J Immunol. 2001;166(4):2695-2704.
Polajeva J, Sjosten AM, Lager N, et al. Mast cell accumulation in glioblastoma with a potential role for stem cell factor and chemokine CXCL12. PLoS One. 2011;6(9):e25222.
Lee A, Kessler JD, Read TA, et al. Isolation of neural stem cells from the postnatal cerebellum. Nat Neurosci. 2005;8(6):723-729.
Mirzadeh Z, Doetsch F, Sawamoto K, et al. The subventricular zone en-face: wholemount staining and ependymal flow. J Vis Exp. 2010;6(39):1938.
Lin F, Baldessari F, Gyenge CC, et al. Lymphocyte electrotaxis in vitro and in vivo. J Immunol. 2008;181(4):2465-2471.
Qiang L, Yang Y, Ma YJ, et al. Isolation and characterization of cancer stem like cells in human glioblastoma cell lines. Cancer Lett. 2009;279(1):13-21.
do Carmo A, Patricio I, Cruz MT, et al. CXCL12/CXCR4 promotes motility and proliferation of glioma cells. Cancer Biol Ther. 2010; 9(1):56-65.
Ehtesham M, Mapara KY, Stevenson CB, et al. CXCR4 mediates the proliferation of glioblastoma progenitor cells. Cancer Lett. 2009; 274(2):305-312.
Burns JM, Summers BC,Wang Y, et al. A novel chemokine receptor for SDF-1 and I-TAC involved in cell survival, cell adhesion, and tumor development. J Exp Med. 2006;203(9):2201-2213.
Hattermann K, Held-Feindt J, Lucius R, et al. The chemokine receptor CXCR7 is highly expressed in human glioma cells and mediates antiapoptotic effects. Cancer Res. 2010;70(8): 3299-3308.
Sun X, Cheng G, Hao M, et al. CXCL12/CXCR4/CXCR7 chemokine axis and cancer progression. Cancer Metastasis Rev. 2010;29(4): 709-722.
Hendrix CW, Flexner C, MacFarland RT, et al. Pharmacokinetics and safety of AMD-3100, a novel antagonist of the CXCR-4 chemokine receptor, in human volunteers. Antimicrob Agents Chemother. 2000;44:1667-1673.
Gerlach LO, Skerlj RT, Bridger GJ, et al. Molecular interactions of cyclam and bicyclam non-peptide antagonists with the CXCR4 chemokine receptor. J Biol Chem. 2001;276(17):14153-14160.
Vooijs M, Jonkers J, Lyons S, et al. Noninvasive imaging of spontaneous retinoblastoma pathway-dependent tumors in mice. Cancer Res. 2002;62(6):1862-1867.
Liu G, Yuan X, Zeng Z, et al. Analysis of gene expression and chemoresistance of CD133+ cancer stem cells in glioblastoma. Mol Cancer. 2006;5(5):67.
Lim YC, Roberts TL, Day BW, et al. A role for homologous recombination and abnormal cell-cycle progression in radioresistance of glioma-initiating cells. Mol Cancer Ther. 2012; 11(9):1863-1872.
Trautmann F, Cojoc M, Kurth I, et al. CXCR4 as Biomarker for Radioresistant Cancer Stem Cells. Int J Radiat Biol. 2014; doi:10.3109/09553002.2014.906766.
Lima FR, Kahn SA, Soletti RC, et al. Glioblastoma: therapeutic challenges, what lies ahead. Biochim Biophys Acta. 2012; 1826(2):338-349.
Lathia JD, Heddleston JM, Venere M, et al. Deadly teamwork: neural cancer stem cells and the tumor microenvironment. Cell Stem Cell. 2011;8(5):482-485.
Alvarez-Buylla A, Lim DA. For the long run: maintaining germinal niches in the adult brain. Neuron. 2004;41(5):683-686.
Evers P, Lee PP, DeMarco J, et al. Irradiation of the potential cancer stem cell niches in the adult brain improves progression-free survival of patients with malignant glioma. BMC Cancer. 2010; 10:384.
Eyler CE, Rich JN. Survival of the fittest: cancer stem cells in therapeutic resistance and angiogenesis. J Clin Oncol. 2008; 26(17):2839-2845.
Bao S, Wu Q, McLendon RE, et al. Glioma stem cells promote radioresistance by preferential activation of the DNA damage response. Nature. 2006;444(7120):756-760.
Jiang Y, Uhrbom L. On the origin of glioma. Ups J Med Sci. 2012; 117(2):113-121.
Goffart N, Kroonen J, Rogister B. Glioblastoma-initiating cells: relationship with neural stem cells and the micro-cnvironment. Cancers (Basel). 2013;5(3):1049-1071.
Lim DA, Cha S, Mayo MC, et al. Relationship of glioblastoma multiforme to neural stem cell regions predicts invasive and multifocal tumor phenotype. Neuro Oncol. 2007;9(4):424-429.
Gatti M, Pattarozzi A, Bajetto A, et al. Inhibition of CXCL12/CXCR4 autocrine/paracrine loop reduces viability of human glioblastoma stem-like cells affecting self-renewal activity. Toxicology. 2013; 314(2-3):209-220.
Gilbertson RJ, Rich JN. Making a tumours bed: glioblastoma stem cells and the vascular niche. Nat Rev Cancer. 2007;7(10):733-736.
Shen Q, Wang Y, Kokovay E, et al. Adult SVZ stem cells lie in a vascular niche: a quantitative analysis of niche cell-cell interactions. Cell Stem Cell. 2008;3(3):289-300.
Tavazoie M, Van der Veken L, Silva-Vargas V, et al. A specialized vascular niche for adult neural stem cells. Cell Stem Cell. 2008; 3(3):279-288.
Galan-Moya EM, Le Guelte A, Lima Fernandes E, et al. Secreted factors from brain endothelial cells maintain glioblastoma stem-like cell expansion through the mTOR pathway. EMBO Rep. 2011;12(5):470-476.
Filipovic R, Zecevic N. The effect of CXCL1 on human fetal oligodendrocyte progenitor cells. Glia. 2008;56(1):1-15.
Liu C, Sage JC, Miller MR, et al. Mosaic analysis with double markers reveals tumor cell of origin in glioma. Cell. 2011;146(2): 209-221.
Micallef IN, Stiff PJ, Stadtmauer EA, et al. Safety and efficacy of upfront plerixafor + G-CSF versus placebo + G-CSF for mobilization of CD34 hematopoietic progenitor cells in patients ≥60 and ,60 years of age with non-Hodgkins lymphoma or multiple myeloma. Am J Hematol. 2013;88:1017-1023.
Dugan MJ, Maziarz RT, Bensinger WI, et al. Safety and preliminary efficacy of plerixafor (Mozobil) in combination with chemotherapy and G-CSF: an open-label, multicenter, exploratory trial in patients with multiple myeloma and non-Hodgkins lymphoma undergoing stem cell mobilization. Bone Marrow Transplant. 2010;45(1):39-47.
Institute D-FC. Plerixafor (AMD3100) and Bevacizumab for Recurrent High-Grade Glioma. Available at: http://clinicaltrials. gov/ct2/show/study/NCT01339039. Accessed April 6, 2011.
