TGF-ß mediates homing of bone marrow-derived human mesenchymal stem cells to glioma stem cells
Shinojima N, Hossain A, Takezaki T, Fueyo J, Gumin J, Gao F, Nwajei F, Marini FC, Andreeff M, Kuratsu J, Lang FF
Cancer Research/Cell Biology
Cells used in publication:
Mesenchymal stem cell (MSC), human
Tissue Origin: bone marrow
Although studies have suggested that bone marrow human mesenchymal stem cells (BM-hMSC) may be used as delivery vehicles for cancer therapy, it remains unclear whether BM-hMSCs are capable of targeting cancer stem cells, including glioma stem cells (GSC), which are the tumor-initiating cells responsible for treatment failures. Using standard glioma models, we identify TGF-ß as a tumor factor that attracts BM-hMSCs via TGF-ß receptors (TGFßR) on BM-hMSCs. Using human and rat GSCs, we then show for the first time that intravascularly administered BM-hMSCs home to GSC-xenografts that express TGF-ß. In therapeutic studies, we show that BM-hMSCs carrying the oncolytic adenovirus Delta-24-RGD prolonged the survival of TGF-ß-secreting GSC xenografts and that the efficacy of this strategy can be abrogated by inhibition of TGFßR on BM-hMSCs. These findings reveal the TGF-ß/TGFßR axis as a mediator of the tropism of BM-hMSCs for GSCs and suggest that TGF-ß predicts patients in whom BM-hMSC delivery will be effective.
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