2014
DOI: 10.1038/cdd.2014.65
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Phage display discovery of novel molecular targets in glioblastoma-initiating cells

Abstract: Glioblastoma is the most common primary intrinsic brain tumor and remains incurable despite maximal therapy. Glioblastomas display cellular hierarchies with self-renewing glioma-initiating cells (GICs) at the apex. To discover new GIC targets, we used in vivo delivery of phage display technology to screen for molecules selectively binding GICs that may be amenable for targeting. Phage display leverages large, diverse peptide libraries to identify interactions with molecules in their native conformation. We del… Show more

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Cited by 27 publications
(30 citation statements)
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References 59 publications
(119 reference statements)
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“…Our classification of these genes as high-malignant or low-malignant is based on their correlation to astrocytoma malignancy and is supported by previous studies. Increased expression of VAV3 in high compared to low grade astrocytoma [ 34 , 35 ], increased NOS2 expression in tumours of higher compared to lower malignancy and in brain tumours compared to healthy tissue [ 36 39 ], and increased SPC24 expression in other tumour types compared to healthy tissue [ 40 ] all support their tumorigenic function. This is emphasized by the negative prognostic effect of VAV3 and NOS2 expression in grade IV astrocytoma and for SPC24 in liver tumours [ 40 ].…”
Section: Discussionmentioning
confidence: 99%
“…Our classification of these genes as high-malignant or low-malignant is based on their correlation to astrocytoma malignancy and is supported by previous studies. Increased expression of VAV3 in high compared to low grade astrocytoma [ 34 , 35 ], increased NOS2 expression in tumours of higher compared to lower malignancy and in brain tumours compared to healthy tissue [ 36 39 ], and increased SPC24 expression in other tumour types compared to healthy tissue [ 40 ] all support their tumorigenic function. This is emphasized by the negative prognostic effect of VAV3 and NOS2 expression in grade IV astrocytoma and for SPC24 in liver tumours [ 40 ].…”
Section: Discussionmentioning
confidence: 99%
“…Expression level of VAV3 in recurrent glioblastoma is higher than that of primary glioblastoma [61]. Elevated VAV3 expression correlates with higher grade tumor and poor prognosis.…”
Section: Biological Library Methodsmentioning
confidence: 99%
“…Targeting VAV3 by ribonucleic acid interference decreased GIC growth, migration, invasion and in vivo tumorigenesis. A VAV3-targeting peptide SSQPFWS was identified by the Rich group through in vivo biopanning of the Ph.D.-7 library in mice implanted subcutaneously with patient-derived glioblastoma xenografts [61]. This peptide specifically internalized into GICs.…”
Section: Biological Library Methodsmentioning
confidence: 99%
“…However, GBM is incurable and patients need to undertake other treatments to prolong the survival and relieve the GBM symptoms. Identifying the GBM biomarkers are significantly crucial for early diagnosis, prognosis and treatment management, and has been extensively reported [339][340][341].…”
Section: The Specificity Test Of Each Ab-sers For Epha2 Epha3 and Egmentioning
confidence: 99%
“…Phage display technology can provide the tools for the isolation of antibodies that bind specifically to the cell and organ-specific biomarkers in their native conformation [341,342]. The generated antibodies can form the basis of therapeutic and diagnostic reagents.…”
Section: The Specificity Test Of Each Ab-sers For Epha2 Epha3 and Egmentioning
confidence: 99%