Glioma tropism of haematopoietic progenitor cells is mediated by CXCL12

G. Tabatabai; O. Bähr; J. Wischhusen; I. Eyüpoglu; J. Rieger; M. Weller; W. Wick

doi:10.1055/s-2005-919652

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Aktuelle Neurologie 2005; 32 - P621
DOI: 10.1055/s-2005-919652

Glioma tropism of haematopoietic progenitor cells is mediated by CXCL12

G Tabatabai ¹, O Bähr ¹, J Wischhusen ¹, I Eyüpoglu ¹, J Rieger ¹, M Weller ¹, W Wick ¹

¹Tubingen

Congress Abstract

Adult stem and progenitor cells (PC) of various tissues are considered as promising candidates to establish a cell-based therapy against cancers, notably glioblastoma. Here we report that adult human and murine hematopoietic PC display a tropism for intracerebral experimental gliomas in vivo but not for normal brain tissue. 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-Ò) synthesis by the glioma cells strongly inhibits PC cell migration. Further migration experiments in vitro delineate a CXC chemokine ligand (CXCL)12-dependent pathway of hematopoietic PC migration that is further enhanced by MMP-9 mediated cleavage of stem cell factor (SCF). Moreover, application of neutralizing antibodies against CXCL12 in vivo strongly reduce PC homing to experimental gliomas. In summary, we investigated the molecular mechanism underlying the glioma tropism of adult hematopoietic PC.