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Vascular Gene Expression in Nonneoplastic and Malignant Brain

Al Musella's Comments: (This is his personal views and are not necessarily the views of the Musella Foundation!)


Posted on: 07/27/2004

Vascular Gene Expression in Nonneoplastic and Malignant Brain

(American Journal of Pathology. 2004;165:601-608.)

© 2004 American Society for Investigative Pathology

Stephen L. Madden*, Brian P. Cook*, Mariana Nacht*, William D. Weber*, Michelle R. Callahan*, Yide Jiang*, Michael R. Dufault*, Xiaoming Zhang*, Wen Zhang*, Jennifer Walter-Yohrling*, Cecile Rouleau*, Viatcheslav R. Akmaev*, Clarence J. Wang*, Xiaohong Cao*, Thia B. St. Martin*, Bruce L. Roberts*, Beverly A. Teicher*, Katherine W. Klinger*, Radu-Virgil Stan, Brenden Lucey, Eleanor B. Carson-Walter¶||, John Laterra and Kevin A. Walter¶||

From Genzyme Oncology,* Framingham, Massachusetts; the Department of Cellular and Molecular Medicine, University of California–San Diego, La Jolla, California; the Department of Neurology, Neuroscience, and Oncology, Johns Hopkins University, Baltimore, Maryland; the Kennedy Krieger Institute, Baltimore, Maryland; the Department of Neurosurgery, ¶ University of Pittsburgh, Pittsburgh, Pennsylvania; and the Brain Tumor Center,|| Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania

Malignant gliomas are uniformly lethal tumors whose morbidity is mediated in large part by the angiogenic response of the brain to the invading tumor. This profound angiogenic response leads to aggressive tumor invasion and destruction of surrounding brain tissue as well as blood-brain barrier breakdown and life-threatening cerebral edema. To investigate the molecular mechanisms governing the proliferation of abnormal microvasculature in malignant brain tumor patients, we have undertaken a cell-specific transcriptome analysis from surgically harvested nonneoplastic and tumor-associated endothelial cells. SAGE-derived endothelial cell gene expression patterns from glioma and nonneoplastic brain tissue reveal distinct gene expression patterns and consistent up-regulation of certain glioma endothelial marker genes across patient samples. We define the G-protein-coupled receptor RDC1 as a tumor endothelial marker whose expression is distinctly induced in tumor endothelial cells of both brain and peripheral vasculature. Further, we demonstrate that the glioma-induced gene, PV1, shows expression both restricted to endothelial cells and coincident with endothelial cell tube formation. As PV1 provides a framework for endothelial cell caveolar diaphragms, this protein may serve to enhance glioma-induced disruption of the blood-brain barrier and transendothelial exchange. Additional characterization of this extensive brain endothelial cell gene expression database will provide unique molecular insights into vascular gene expression.

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