Lessons from the bone marrow: how malignant glioma cells attract adult haematopoietic progenitor cells

Stem and progenitor cells (PCs) of various lineages have become attractive vehicles to improve therapeutic gene delivery to cancers, notably glioblastoma. Here we report that adult human and murine haematopoietic PCs display a tropism for intracerebral gliomas but not for normal brain tissue in mice...

Ausführliche Beschreibung

Gespeichert in:

Bibliographische Detailangaben
Veröffentlicht in:	Brain (London, England : 1878) England : 1878), 2005-09, Vol.128 (9), p.2200-2211
Hauptverfasser:	Tabatabai, Ghazaleh, Bähr, Oliver, Möhle, Robert, Eyüpoglu, Ilker Y., Boehmler, Andreas M., Wischhusen, Jörg, Rieger, Johannes, Blümcke, Ingmar, Weller, Michael, Wick, Wolfgang
Format:	Artikel
Sprache:	eng
Schlagworte:	Adult Animals Biological and medical sciences Brain Neoplasms - metabolism Brain Neoplasms - pathology CA1 = cornu ammonis 1 CA3 = cornu ammonis 3 CD117 = cluster of differentiation 117 CD34+PC = G-CSF mobilized peripheral blood CD34+ progenitor and stem cells CFSE = carbofluorescein diacetate succinimidyl ester Chemokine CXCL12 Chemokines, CXC - physiology Chemotaxis CXCL12 CXCL12 = CXC chemokine ligand CXCR4 = chemokine receptor 4 Development. Senescence. Regeneration. Transplantation DG = dentate gyrus EC = entorhinal cortex FCS = fetal calf serum Fundamental and applied biological sciences. Psychology G-CSF = granulocyte colony stimulating factor Glioma - metabolism Glioma - pathology HBSS = Hanks' balanced salt solution Hematopoietic Stem Cell Transplantation Hematopoietic Stem Cells - cytology hippocampal slice culture Humans Isolated neuron and nerve. Neuroglia lin− = lineage-depleted MACS = magnetic activated cell sorting Matrix Metalloproteinase 9 - physiology Medical sciences metalloproteinase Mice Mice, Nude MMP = matrix metalloproteinase Neoplasm Transplantation Neurology nu PC = bone marrow-derived murine lin−Sca1+ haematopoietic stem and progenitor and lin− stem and progenitor cells from athymic nude mice PKB = protein kinase B RO28-2653 = 5-biphenyl-4-yl-5-[4-(nitro-phenyl)-piperazin-1-yl]-pyrimidine-2 SC = stem cell sca1 = stem cell antigen SCF = stem cell factor SDF = stromal cell-derived factor SEM = standard error of the mean SFM = serum-free medium sKitL = soluble Kit ligand Stem Cell Factor - physiology TGF = transforming growth factor TGF-β Transforming Growth Factor beta - physiology Tumor Cells, Cultured Vertebrates: nervous system and sense organs VM/Dk PC = bone marrow-derived murine lin−Sca1+ haematopoietic stem and lin− stem and progenitor cells from immunocompetent VM/Dk mice
Online-Zugang:	Volltext
Tags:	Tag hinzufügen Keine Tags, Fügen Sie den ersten Tag hinzu!

Beschreibung
Zusammenfassung:	Stem and progenitor cells (PCs) of various lineages have become attractive vehicles to improve therapeutic gene delivery to cancers, notably glioblastoma. Here we report that adult human and murine haematopoietic PCs display a tropism for intracerebral gliomas but not for normal brain tissue in mice. Organotypic hippocampal slice culture and spheroid confrontation assays confirm a directed PC migration towards glioma cells ex vivo and in vitro. RNA interference-mediated disruption of transforming growth factor beta (TGF-β) synthesis by the glioma cells strongly inhibits PC migration. We delineate a CXC chemokine ligand (CXCL) 12-dependent pathway of TGF-β-induced PC migration that is facilitated by MMP-9-mediated stem cell factor cleavage in vitro. Moreover, neutralizing antibodies to CXCL12 strongly reduce PC homing to experimental gliomas in vivo. Thus, we define here the molecular mechanism underlying the glioma tropism of the probably most easily accessible PC population suitable for cancer therapy, that is, adult haematopoietic PC.
ISSN:	0006-8950 1460-2156
DOI:	10.1093/brain/awh563