Expression of a-disintegrin and metalloproteinase 10 correlates with grade of malignancy in human glioma

Qu, Min; Qiu, Bo; Xiong, Wen-de; Chen, Dong; Wu, Anhua

doi:10.3892/ol.2015.2993

Cited by 19 publications

(15 citation statements)

References 35 publications

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“…ADAM10 is expressed in gliomas as reported in the literature 21,22 and demonstrated in gene expression datasets from pediatric and adult HGG samples (Extended Data Fig. 5d).…”

supporting

confidence: 73%

Targeting neuronal activity-regulated neuroligin-3 dependency in high-grade glioma

Venkatesh

Tam

Woo

et al. 2017

Nature

389

374

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Summary High-grade gliomas (HGG) are a devastating group of cancers, representing the leading cause of brain tumor-related death in both children and adults. Therapies aimed at mechanisms intrinsic to the glioma cell have translated to only limited success; effective therapeutic strategies will need to also target elements of the tumor microenvironment that promote glioma progression. We recently demonstrated that neuronal activity robustly promotes the growth of a range of molecularly and clinically distinct HGG types, including adult glioblastoma (GBM), anaplastic oligodendroglioma, pediatric GBM, and diffuse intrinsic pontine glioma (DIPG)1. An important mechanism mediating this neural regulation of brain cancer is activity-dependent cleavage and secretion of the synaptic molecule neuroligin-3 (NLGN3), which promotes glioma proliferation through the PI3K-mTOR pathway1. However, neuroligin-3 necessity to glioma growth, proteolytic mechanism of secretion and further molecular consequences in glioma remain to be clarified. Here, we demonstrate a striking dependence of HGG growth on microenvironmental neuroligin-3, elucidate signaling cascades downstream of neuroligin-3 binding in glioma and determine a therapeutically targetable mechanism of secretion. Patient-derived orthotopic xenografts of pediatric GBM, DIPG and adult GBM fail to grow in Nlgn3 knockout mice. Neuroligin-3 stimulates numerous oncogenic pathways, including early focal adhesion kinase activation upstream of PI3K-mTOR, and induces transcriptional changes including upregulation of numerous synapse-related genes in glioma cells. Neuroligin-3 is cleaved from both neurons and oligodendrocyte precursor cells via the ADAM10 sheddase. ADAM10 inhibitors prevent release of neuroligin-3 into the tumor microenvironment and robustly block HGG xenograft growth. This work defines a promising strategy for targeting neuroligin-3 secretion, which could prove transformative for HGG therapy.

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“…ADAM10 is expressed in gliomas as reported in the literature 21,22 and demonstrated in gene expression datasets from pediatric and adult HGG samples (Extended Data Fig. 5d).…”

supporting

confidence: 73%

Targeting neuronal activity-regulated neuroligin-3 dependency in high-grade glioma

Venkatesh

Tam

Woo

et al. 2017

Nature

389

374

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“…ADAM10 has mainly been reported in cell membranes and blood vessel walls. In high-grade gliomas, the ADAM10 expression is significantly higher than in grade I/II gliomas and in the control group [83]. Similar findings were reported for ADAM9.…”

Section: Brain Tumorssupporting

confidence: 83%

ADAM protein family – its role in tumorigenesis, mechanisms of chemoresistance and potential as diagnostic and prognostic factors

Zadka

Kulus

Piątek

2018

neo

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ADAMs are a family of transmembrane proteins described for the first time in the 1990's. ADAMs is an abbreviation of "A Disintegrin and Metallo-proteinases". Their earliest known role was involvement in gamete fusion, and their adhesion properties in intercellular interactions also suggested involvement in tumor biology. Further research emphasized the importance of ADAM proteins in the regulation of neoplastic processes due to their influence on adhesion, cell migration, proteolysis and cell signaling. Variable ADAM expression in cancer and normal tissue was the basis for considering these proteins as diagnostic markers. Recent numerous studies have been published suggesting the prognostic value of this protein family members. The ADAMs transmembrane proteins regulate processes associated with carcinogenesis and neoplastic progression, including immune response evasion, growth induction and metastasis. Proteolysis and shedding of membrane proteins and binding integrins by ADAMs lead to the activation of numerous growth factors, changes in the extracellular matrix, adhesion proteins and angiogenesis. ADAMs potential as prognostic and diagnostic markers in cancer treatment is a particularly interesting issue and has great practical significance. There are many new studies concerning ADAMs' roles in carcinogenesis, but there are no recent reviews of the latest developments in this field. The aim of this systematic review is to analyze the results of studies published on ADAMs in the last 5 years, to present their roles in neoplasm pathogenesis and their potential utility in clinical oncology.

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“…As ADAM10 is a key mediator of Nlgn3 secretion, and we have shown the importance of Nlgn3 for high-grade glioma growth in vivo, we investigated the therapeutic potential of ADAM10 inhibition for HGG. ADAM10 is expressed in gliomas as reported in the literature 24,25 and demonstrated in gene expression datasets from pediatric and adult HGG samples 1,16,26–28 (Extended Data Fig. 7d).…”

Section: Adam10 Inhibition Blocks Glioma Growth In Vivosupporting

confidence: 69%

Targeting neuronal activity-regulated neuroligin-3 dependency for high-grade glioma therapy

et al. 2017

Preprint

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Abstract:Neuronal activity promotes high-grade glioma (HGG) growth. An important mechanism mediating this neural regulation of brain cancer is activity-dependent cleavage and secretion of the synaptic molecule and glioma mitogen neuroligin-3 (Nlgn3), but the therapeutic potential of targeting Nlgn3 in glioma remains to be defined. We demonstrate a striking dependence of HGG growth on microenvironmental Nlgn3 and determine a targetable mechanism of secretion.Patient-derived orthotopic xenografts of pediatric glioblastoma, diffuse intrinsic pontine glioma peer-reviewed) is the author/funder. All rights reserved. No reuse allowed without permission.The copyright holder for this preprint (which was not . http://dx.doi.org/10.1101/153122 doi: bioRxiv preprint first posted online Jun. 21, 2017; derived neurotrophic factor (Bdnf) and neuroligin-3 (Nlgn3) into the tumor microenvironment 1 .

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Expression of a-disintegrin and metalloproteinase 10 correlates with grade of malignancy in human glioma

Cited by 19 publications

References 35 publications

Targeting neuronal activity-regulated neuroligin-3 dependency in high-grade glioma

Targeting neuronal activity-regulated neuroligin-3 dependency in high-grade glioma

ADAM protein family – its role in tumorigenesis, mechanisms of chemoresistance and potential as diagnostic and prognostic factors

Targeting neuronal activity-regulated neuroligin-3 dependency for high-grade glioma therapy

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