| Literature DB >> 15947066 |
Ghazaleh Tabatabai1, Oliver Bähr, Robert Möhle, Ilker Y Eyüpoglu, Andreas M Boehmler, Jörg Wischhusen, Johannes Rieger, Ingmar Blümcke, Michael Weller, Wolfgang Wick.
Abstract
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-beta) synthesis by the glioma cells strongly inhibits PC migration. We delineate a CXC chemokine ligand (CXCL) 12-dependent pathway of TGF-beta-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.Entities:
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Year: 2005 PMID： 15947066 DOI： 10.1093/brain/awh563
Source DB: PubMed Journal: Brain ISSN： 0006-8950 Impact factor: 13.501