Vascular gene expression in nonneoplastic and malignant brain.
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.
Madden
Stephen L
SL
Genetics and Genomics, 5 Mountain Rd., Framingham, MA 01701, USA. steve.madden@genzyme.com.
Cook
Brian P
BP
Nacht
Mariana
M
Weber
William D
WD
Callahan
Michelle R
MR
Jiang
Yide
Y
Dufault
Michael R
MR
Zhang
Xiaoming
X
Zhang
Wen
W
Walter-Yohrling
Jennifer
J
Rouleau
Cecile
C
Akmaev
Viatcheslav R
VR
Wang
Clarence J
CJ
Cao
Xiaohong
X
St  Martin
Thia B
TB
Roberts
Bruce L
BL
Teicher
Beverly A
BA
Klinger
Katherine W
KW
Stan
Radu-Virgil
RV
Lucey
Brenden
B
Carson-Walter
Eleanor B
EB
Laterra
John
J
Walter
Kevin A
KA
D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D001921:Brain / Q000098:blood supply; D001932:Brain Neoplasms / Q000098:blood supply* / Q000378:metabolism* / Q000473:pathology; D004730:Endothelium, Vascular / Q000378:metabolism* / Q000473:pathology; D005910:Glioma / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D009389:Neovascularization, Pathologic / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
D014408:Biomarkers, Tumor; D012333:RNA, Messenger