Structural and expression differences between the vasculature of pilocytic astrocytomas and glioblastomas.
The identification of differences in vascular architecture and utilization of angiogenic pathways is a first step for identifying specific targets for tailored antiangiogenic therapies of brain tumor patients. Here, we compared the proliferating vasculature of 2 glioma subtypes with entirely different biologic behaviors and molecular background at the immunophenotype and gene expression levels. Proliferating vessels in 13 pilocytic astrocytomas and 8 glioblastomas were compared for differences in the composition of the vascular walls using confocal microscopy for markers of endothelial cells and pericytes/mural cells. Endothelial, pericytic, and mural cells had normal-appearing arrangements in the vessels in pilocytic astrocytomas, whereas those in glioblastomas appeared to be more disorganized. In addition, differences in expression of angiogenesis-related genes were sought in the tumor specimens using RNA expression arrays. There were 114 out of 2,894 differentially expressed angiogenesis-related genes between these 2 glioma subtypes indicating differences in the utilization of various pathways. These results point to the need for detailed information on mechanisms of neoangiogenesis in tumor subtypes to facilitate the development of specific antiangiogenic strategies.
From the Departments of Pathology (DM, JMK), BioInformatics (SS, PvdS, AK), and Neurology (PF, TML), Erasmus Medical Center, Rotterdam, The Netherlands.
Dana
D
Mustafa
Sigrid
S
Swagemakers
Pim
P
French
Theodorus M
TM
Luider
Peter
P
van der Spek
Andreas
A
Kremer
Johan M
JM
Kros
D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000378:metabolism; D001254:Astrocytoma / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D001932:Brain Neoplasms / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D002352:Carrier Proteins / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D000071063:Endoglin; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D005909:Glioblastoma / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D006023:Glycoproteins; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D007223:Infant; D007521:Isocitrate Dehydrogenase / Q000378:metabolism; D008297:Male; D018613:Microscopy, Confocal; D008875:Middle Aged; D020286:Pericytes / Q000378:metabolism / Q000473:pathology*; D011956:Receptors, Cell Surface / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D055815:Young Adult
D015703:Antigens, CD; D002352:Carrier Proteins; C064206:ENG protein, human; D000071063:Endoglin; D006023:Glycoproteins; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D011956:Receptors, Cell Surface; D042461:Vascular Endothelial Growth Factor A; C046289:colligin; D007521:Isocitrate Dehydrogenase