A small-molecule antagonist of CXCR4 inhibits intracranial growth of primary brain tumors

Proceedings of the National Academy of Sciences of the United States of America - Tập 100 Số 23 - Trang 13513-13518 - 2003
Joshua B. Rubin1, Andrew L. Kung1, Robyn S. Klein2,3,1, Jennifer A. Chan3,1, Yanping Sun2,3,1, Karl Schmidt1, Mark W. Kieran1, Andrew D. Luster4,1, Rosalind A. Segal3,1
1Departments of Pediatric Oncology and Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02115; Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital, Charlestown, MA 02129; Department of Pathology, Children's Hospital, Boston, MA 02115;Department of Radiology, Brigham and Women's Hospital, Boston, MA 02115; and Department of Neurobiology, Harvard Medical School, Boston, MA 02115
2Department of Neurobiology, Harvard Medical School, Boston, MA 02115.
3Department of Pathology, Children's Hospital, Boston, MA 02115.
4Department of Radiology, Brigham and Women's Hospital, Boston, MA 02115; and

Tóm tắt

The vast majority of brain tumors in adults exhibit glial characteristics. Brain tumors in children are diverse: Many have neuronal characteristics, whereas others have glial features. Here we show that activation of the Giprotein-coupled receptor CXCR4 is critical for the growth of both malignant neuronal and glial tumors. Systemic administration of CXCR4 antagonist AMD 3100 inhibits growth of intracranial glioblastoma and medulloblastoma xenografts by increasing apoptosis and decreasing the proliferation of tumor cells. This reflects the ability of AMD 3100 to reduce the activation of extracellular signal-regulated kinases 1 and 2 and Akt, all of which are pathways downstream of CXCR4 that promote survival, proliferation, and migration. These studies (i) demonstrate that CXCR4 is critical to the progression of diverse brain malignances and (ii) provide a scientific rationale for clinical evaluation of AMD 3100 in treating both adults and children with malignant brain tumors.

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Proceedings of the National Academy of Sciences of the United States of America

Tập 100 Số 23

13513-13518

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