• Naoki Shinojima, Anwar Hossain, Tatsuya Takezaki, Juan Fueyo, Joy Gumin, Feng Gao, Felix Nwajei, Frank C Marini, Michael Andreeff, Jun-Ichi Kuratsu, and Frederick F Lang.
• Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
• Cancer Res. 2013 Apr 1; 73 (7): 2333-44.

AbstractAlthough 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-β as a tumor factor that attracts BM-hMSCs via TGF-β receptors (TGFβR) 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-β. In therapeutic studies, we show that BM-hMSCs carrying the oncolytic adenovirus Delta-24-RGD prolonged the survival of TGF-β-secreting GSC xenografts and that the efficacy of this strategy can be abrogated by inhibition of TGFβR on BM-hMSCs. These findings reveal the TGF-β/TGFβR axis as a mediator of the tropism of BM-hMSCs for GSCs and suggest that TGF-β predicts patients in whom BM-hMSC delivery will be effective.©2012 AACR.

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