Neoplastic Cells are a Rare Component in Human Glioblastoma Microvasculature

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Neoplastic Cells are a Rare Component in Human Glioblastoma Microvasculature

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dc.contributor.author Rodriguez, Fausto J.
dc.contributor.author Orr, Brent A.
dc.contributor.author Eberhart, Charles G.
dc.contributor.author Ligon, Keith Lloyd
dc.date.accessioned 2012-04-24T17:57:39Z
dc.date.issued 2012
dc.identifier.citation Rodriguez, Fausto J., Brent A. Orr, Keith L. Ligon, and Charles G. Eberhart. 2012. Neoplastic cells are a rare component in human glioblastoma microvasculature. Oncotarget 3(1): 98-106. en_US
dc.identifier.issn 1949-2553 en_US
dc.identifier.uri http://nrs.harvard.edu/urn-3:HUL.InstRepos:8609126
dc.description.abstract Microvascular proliferation is a key biological and diagnostic hallmark of human glioblastoma, one of the most aggressive forms of human cancer. It has recently been suggested that stem-like glioblastoma cells have the capacity to differentiate into functional endothelial cells, and that a significant proportion of the vascular lining in tumors has a neoplastic origin. In principle, this finding could significantly impact the efficacy and development of antiangiogenic therapies targeting the vasculature. While the potential of stem-like cancer cells to form endothelium in culture seems clear, in our clinical experience using a variety of molecular markers, neoplastic cells do not contribute significantly to the endothelial-lined vasculature of primary human glioblastoma. We sought to confirm this impression by analyzing vessels in glioblastoma previously examined using chromogenic in situ hybridization (CISH) for EGFR and immunohistochemistry for mutant IDH1. Vessels containing cells expressing these definitive neoplastic markers were identified in a small fraction of tumors, but only 10% of vessel profiles examined contained such cells and when identified these cells comprised less than 10% of the vascular cellularity in the cross section. Interestingly, these rare intravascular cells showing EGFR amplification by CISH or mutant IDH1 protein by immunohistochemistry were located in the middle or outer portions of vessel walls, but not amongst the morphologic boundaries of the endothelial lining. To more directly address the capacity of glioblastoma cells to contribute to the vascular endothelium, we performed double labeling (Immunofluorescence/FISH) for the endothelial marker CD34 and EGFR gene locus. Although rare CD34 positive neoplastic cells unassociated with vessels were identified (<1%), this analysis did not identify EGFR amplified cells within vascular linings, and further supports our observations that incorporation of glioblastoma cells into the tumor vessels is at best extremely rare, and therefore of questionable clinical or therapeutic significance. en_US
dc.language.iso en_US en_US
dc.publisher Impact Journals LLC en_US
dc.relation.isversionof http://www.impactjournals.com/oncotarget/index.php?journal=oncotarget en_US
dc.relation.hasversion http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3292896/pdf/ en_US
dash.license LAA
dc.subject glioblastoma en_US
dc.subject microvascular proliferation en_US
dc.subject endothelium en_US
dc.subject stem cells en_US
dc.subject FISH en_US
dc.title Neoplastic Cells are a Rare Component in Human Glioblastoma Microvasculature en_US
dc.type Journal Article en_US
dc.description.version Version of Record en_US
dc.relation.journal Oncotarget en_US
dash.depositing.author Ligon, Keith Lloyd
dc.date.available 2012-04-24T17:57:39Z

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