Delta-Like Ligand 4 Correlates with Endothelial Proliferation and Vessel Maturation in Human Malignant Glioma

Li, Zhiqiang; Gong, Ling; Wen, Zhi‐Hong; Wang, Jiang; Xu, Congcong; Huang, Xiao-Dong

doi:10.1159/000345116

Cited by 12 publications

(8 citation statements)

References 27 publications

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“…60,61,67,68,120,131,[135][136][137] However, in several cases, MVD is positively associated with DLL4 expression, which contradicts the effects of DLL4 on inhibiting neovascularization. [39][40][41]50,63,75,83,92,97,98,138,139 Herein, we discuss the possible mechanisms responsible for DLL4-induced functional and productive angiogenesis, and for the first time describe the potential effects of DLL4 on promoting tumor neovascularization.…”

Section: Dll4 In Tumor Vasculaturementioning

confidence: 99%

<p>The Role of DLLs in Cancer: A Novel Therapeutic Target</p>

Xiu

Liu

Kuang

2020

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Delta-like ligands (DLLs) control Notch signaling. DLL1, DLL3 and DLL4 are frequently deregulated in cancer and influence tumor growth, the tumor vasculature and tumor immunity, which play different roles in cancer progression. DLLs have attracted intense research interest as anti-cancer therapeutics. In this review, we discuss the role of DLLs in cancer and summarize the emerging DLL-relevant targeting methods to aid future studies.

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Section: Dll4 In Tumor Vasculaturementioning

confidence: 99%

<p>The Role of DLLs in Cancer: A Novel Therapeutic Target</p>

Xiu

Liu

Kuang

2020

OTT

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“…S1 and S2). Endothelial laminin-411 interacts with the Notch system through the integrin-Dll4 pathway (15,16,30). To determine whether this interaction was functional in normal brain cells and gliomas, we conducted in vitro experiments to test the influence of the ECM on Notch system in NHA, HBMVEC, and cultured human GBM cell lines LN229 and U87MG.…”

Section: Laminin-411 Upregulates the B1 Integrin-notch Pathway In Hummentioning

confidence: 99%

Blockade of a Laminin-411–Notch Axis with CRISPR/Cas9 or a Nanobioconjugate Inhibits Glioblastoma Growth through Tumor-Microenvironment Cross-talk

et al. 2019

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There is an unmet need for the treatment of glioblastoma multiforme (GBM). The extracellular matrix, including laminins, in the tumor microenvironment is important for tumor invasion and progression. In a panel of 226 patient brain glioma samples, we found a clinical correlation between the expression of tumor vascular laminin-411 (a4b1g1) with higher tumor grade and with expression of cancer stem cell (CSC) markers, including Notch pathway members, CD133, Nestin, and c-Myc. Laminin-411 overexpression also correlated with higher recurrence rate and shorter survival of GBM patients. We also showed that depletion of laminin-411 a4 and b1 chains with CRISPR/Cas9 in human GBM cells led to reduced growth of resultant intracranial tumors in mice and significantly increased survival of host animals compared with mice with untreated cells. Inhibition of laminin-411 suppressed Notch pathway in normal and malignant human brain cell types. A nanobioconjugate potentially suitable for clinical use and capable of crossing blood-brain barrier was designed to block laminin-411 expression. Nanobioconjugate treatment of mice carrying intracranial GBM significantly increased animal survival and inhibited multiple CSC markers, including the Notch axis. This study describes an efficient strategy for GBM treatment via targeting a critical component of the tumor microenvironment largely independent of heterogeneous genetic mutations in glioblastoma. Significance: Laminin-411 expression in the glioma microenvironment correlates with Notch and other cancer stem cell markers and can be targeted by a novel, clinically translatable nanobioconjugate to inhibit glioma growth.

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“…It is not surprising then that EphB4/ephrin-B2 expression has been detected in GBM and linked to tumour angiogenesis ( Xiao et al , 2004 ; Erber et al , 2006 ; Chen et al , 2013 ). EphB4 has been shown to promote venous angiogenesis via the DLL-4-Notch signalling pathway ( Li et al , 2011 , 2012 ), whereas ephrin-B2 promotes arterial angiogenesis through regulation of VEGFR2 function ( Sawamiphak et al , 2010 ). Expression of these proteins has also been positively correlated with GBM progression and poor prognosis ( Tu et al , 2012 ).…”

Section: Eph and Ephrin Expression And Function In Gbmmentioning

confidence: 99%

Eph receptors as therapeutic targets in glioblastoma

2014

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The dismal outlook for patients with the most aggressive and common form of adult brain cancer, glioblastoma (GBM), motivates a search for new therapeutic strategies and targets for this aggressive disease. Here we review the findings to date on the role of Eph family receptor tyrosine kinases and their ephrin ligands in brain cancer. Expression of the Eph family of cell surface proteins is generally downregulated to very low levels in normal adult tissues making them particularly attractive for directed therapeutic targeting. Recent Eph targeting studies in pre-clinical models of GBM have been very encouraging and may provide an avenue to treat these highly refractory aggressive tumours.

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Delta-Like Ligand 4 Correlates with Endothelial Proliferation and Vessel Maturation in Human Malignant Glioma

Cited by 12 publications

References 27 publications

<p>The Role of DLLs in Cancer: A Novel Therapeutic Target</p>

<p>The Role of DLLs in Cancer: A Novel Therapeutic Target</p>

Blockade of a Laminin-411–Notch Axis with CRISPR/Cas9 or a Nanobioconjugate Inhibits Glioblastoma Growth through Tumor-Microenvironment Cross-talk

Eph receptors as therapeutic targets in glioblastoma

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