CXCR4-Mediated Glioma Tumor Tracking by Bone Marrow-Derived Neural Progenitor/Stem Cells

• Published in: Molecular cancer therapeutics 2009-09, Vol.8 (9), p.2746-2753
• Main Authors: Xu, Qijin, Yuan, Xiangpeng, Xu, Minlin, McLafferty, Fred, Hu, Jinwei, Lee, Bong Seop, Liu, Gentao, Zeng, Zhaohui, Black, Keith L., Yu, John S.
• Format: Article
• Language: English
• ISSN: 1535-7163; 1538-8514
• DOI: 10.1158/1535-7163.MCT-09-0273

Malignant gliomas manifest frequent tumor recurrence after surgical resection and/or other treatment, due to its nature of invasiveness and dissemination. The recognized brain tumor-tracking property of neural progenitor/stem cells (NSCs) opened the possibility of targeting malignant brain tumors using NSCs. We and others have previously demonstrated that fetal NSCs can be utilized to deliver therapeutic molecules to brain tumors. Our recent work has further shown that gene delivery by bone marrow-derived NSCs (BM-NSCs) achieves therapeutic effects in a glioma model. In this study, we isolate and characterize BM-NSCs which also express the chemokine receptor CXCR4. We show that CXCR4 is required for their chemotaxis and extracelluilar matrix invasion against a gradient of glioma soluble factors. Furthermore, LacZ-labeled BM-NSCs implanted in the contralateral side of the brain were shown to track gliomas as early as day 1, and increased through day 3 and day 7. Intracranial glioma tracking by BM-NSCs is significantly inhibited by pre-incubation of BM-NSCs with a blocking anti-CXCR4 antibody, suggesting a CXCR4-dependent tracking mechanism. Glioma tracking BM-NSCs were found to express progenitor/stem cell markers, as well as CXCR4. Although BrdU incorporation assays and proliferating antigen staining indicated that tumor tracking BM-NSCs were mostly non-proliferating, these cells survive in the local tumor environment with little apoptosis. Elucidating the molecular mechanism of brain tumor tracking by adult source stem cells may provide basis for the development of future targeted therapy for malignant brain tumors.