Molecular markers of extracellular matrix remodeling in glioblastoma vessels: microarray study of laser-captured glioblastoma vessels.
Glioblastoma multiforme (GBM) are the most malignant and vascularized brain tumors. The aberrant vascular phenotype of GBM could be exploited for diagnosis or therapeutic targeting. This study identified new molecular markers of GBM vessels, using a combination of laser capture microdissection (LCM) microscopy, RNA amplification, and microarray analyses to compare vessels from nonmalignant human brain and GBM tumors. Forty-two genes were differentially expressed in GBM vessels compared to nonmalignant brain vessels. Validation of differentially expressed genes was performed by literature mining, Q-PCR, and immunohistochemistry. Among the differentially expressed genes, only 64% were previously associated with vessels, angiogenesis, gliomas, and/or cancer. The upregulation of genes encoding secreted extracellular proteins IGFBP7 and SPARC was confirmed by Q-PCR in LCM-captured vessels. Whereas SPARC and IGFBP7 protein were absent in nonmalignant brain vessels, a distinct immunoreactivity patterns were observed in GBM sections whereby SPARC was strongly expressed in perivascular cells adjacent to GBM vessels while GBM endothelial cells were immunostained for IGFBP7. IGFBP7 immunoreactivity was also detected on the abluminal side of GBM vessels deposited between strands of vascular basal lamina. The study discerns unique molecular characteristics of GBM vessels compared with nonmalignant brain vessels that could potentially be used for diagnostic or therapeutic purposes.
Pen
Ally
A
Cerebrovascular Research Group, Neurobiology Program, Institute for Biological Sciences, National Research Council of Canada, Ottawa, Ontario, Canada.
Moreno
Maria J
MJ
Martin
Joel
J
Stanimirovic
Danica B
DB
D001485:Basement Membrane / Q000378:metabolism / Q000648:ultrastructure; D014408:Biomarkers, Tumor / Q000235:genetics*; D001932:Brain Neoplasms / Q000098:blood supply* / Q000503:physiopathology; D002536:Cerebral Arteries / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D042783:Endothelial Cells / Q000378:metabolism / Q000648:ultrastructure; D016326:Extracellular Matrix Proteins / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D005909:Glioblastoma / Q000098:blood supply* / Q000503:physiopathology; D006801:Humans; D018969:Insulin-Like Growth Factor Binding Proteins / Q000235:genetics; D007834:Lasers; D042282:Microdissection / Q000295:instrumentation / Q000379:methods; D009389:Neovascularization, Pathologic / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D015676:Osteonectin / Q000235:genetics; D012313:RNA / Q000032:analysis / Q000378:metabolism
D014408:Biomarkers, Tumor; D016326:Extracellular Matrix Proteins; D018969:Insulin-Like Growth Factor Binding Proteins; D015676:Osteonectin; C102529:insulin-like growth factor binding protein-related protein 1; D012313:RNA