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Journal of Child Neurology
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Targeting Hyaluronan Interactions in Spinal Cord Astrocytomas and Diffuse Pontine Gliomas

Bernard L. Maria, MD, MBA

Departments of Pediatrics and Neurosciences, Charles P. Darby Children's Research Institute, College of Medicine, Medical University of South Carolina, Charleston, South Carolina, mariabl{at}musc.edu

Nalin Gupta, MD, PhD

Department of Neurosurgery, University of California, San Francisco

Anne G. Gilg, PhD

Department of Pediatrics, Charles P. Darby Children's Research Institute, College of Medicine, Medical University of South Carolina, Charleston, South Carolina

May Abdel-Wahab, MD

Department of Radiation Oncology, University of Miami

Anthony P. Leonard, BS

College of Medicine, Medical University of South Carolina, Charleston, South Carolina

Mark Slomiany, PhD

Department of Cell Biology and Anatomy, Charles P. Darby Children's Research Institute, College of Medicine, Medical University of South Carolina, Charleston, South Carolina

William G. Wheeler, BS

Department of Pediatrics, Charles P. Darby Children's Research Institute, College of Medicine, Medical University of South Carolina, Charleston, South Carolina

Lauren B. Tolliver, MS

Department of Pediatrics, Charles P. Darby Children's Research Institute, College of Medicine, Medical University of South Carolina, Charleston, South Carolina

Michael A. Babcock, BS

College of Medicine, Medical University of South Carolina, Charleston, South Carolina

John T. Lucas, Jr, BS

College of Medicine, Medical University of South Carolina, Charleston, South Carolina

Bryan P. Toole, PhD

Department of Cell Biology and Anatomy, Charles P. Darby Children's Research Institute, College of Medicine, Medical University of South Carolina, Charleston, South Carolina

Although significant advances have been made in treating malignant pediatric central nervous system tumors such as medulloblastoma, no effective therapy exists for diffuse pontine glioma or intramedullary spinal astrocytoma. Biology of these 2 tumors is poorly understood, in part because diffuse pontine gliomas are not treated surgically, and tumor specimens from intramedullary spinal astrocytomas are rare and minuscule. At the 2007 Neurobiology of Disease in Children Symposium, we presented evidence that malignant glioma behaviors, including antiapoptosis, invasiveness, and treatment resistance, are enhanced by hyaluronan, an extracellular glycosaminoglycan. We review the clinical course of pediatric intramedullary spinal astrocytoma and diffuse pontine glioma, and show expression of membrane proteins that interact with hyaluronan: CD44, extracellular matrix metalloproteinase inducer, and breast cancer resistance protein (BCRP/ABCG2). Furthermore, we describe novel animal models of these tumors for preclinical studies. These findings suggest that hyaluronan antagonism has potential therapeutic value in malignant central nervous system tumors.

Key Words: hyaluronan • glioma • astrocytoma

References

Journal of Child Neurology, Vol. 23, No. 10, 1214-1220 (2008)
DOI: 10.1177/0883073808321771
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This Article
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