CD90 determined two subpopulations of glioma-associated mesenchymal stem cells with different roles in tumour progression

Zhang, Qing; Yi, Dong-Ye; Xue, Bing-Zhou; Wen, Wanwan; Lu, Yinping; Abdelmaksou, Ahmed; Sun, Minxuan; Yuan, Detian; Zhao, Hongyang; Xiong, Nanxiang; Xiang, Wei; Fu, Peng

doi:10.1038/s41419-018-1140-6

Cited by 32 publications

(67 citation statements)

References 36 publications

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“…VEGF is a crucial cytokine for stimulating angiogenesis of vascular endothelial cells and maintaining the stability of tube structure. Prior studies confirmed that VEGF secreted by tumor cells contributes to promoting tumor angiogenesis [ 30 ]. To examine the effect of viral infection on VEGF production in glioma cells, ELISAs were performed on conditioned media collected from GL261, U251, and U87 glioma cells and primary cells BT-01 after infection with OAd at a certain multiplicity of infection.…”

Section: Resultsmentioning

confidence: 98%

Efficacy of a novel double-controlled oncolytic adenovirus driven by the Ki67 core promoter and armed with IL-15 against glioblastoma cells

Zhang

Tian

et al. 2020

Cell Biosci

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Background Glioblastoma (GBM) is an immunosuppressive, highly vascular and devastating malignant brain tumor. Even with progressive combination treatment that includes surgery, radiotherapy, and chemotherapy, the prognosis for GBM patients is still extremely poor. Oncolytic adenovirus (OAd) can specifically replicate in GBM cells, permitting the rapid copy of the therapeutic genes it carries. Moreover, E1A is an essential gene in adenoviral replication and is the first gene expressed upon viral infection. E1A expression can be regulated by the Ki67 promoter, while the CMV promoter drives therapeutic gene expression. However, the efficacy of a double-controlled OAd driven by the Ki67 core promoter and armed with IL-15 against GBM cells has not been investigated. Methods Fluorescence microscopy was performed to evaluate infection ability in the viruses. Cell viability was detected by CCK-8 assay. Levels of cytokines in different supernatants were determined by ELISA, and IL-15 gene expression was measured by RT-PCR. Angiogenic capacity was analyzed by tube formation assay. Results We successfully constructed a double-controlled oncolytic adenovirus driven by the Ki67 core promoter and armed with IL-15 that selectively infected and killed GBM cells while sparing normal cells. The adenoviruses prime IL-15 gene expression to significantly enhance anti-GBM efficacy through effective activation of microglial cells. Moreover, OAd not only directly inhibits angiogenesis but exhibits potent antiangiogenic capacity mediated by the reduction of VEGF secretion. Conclusions These results provide new insight into the effects of a novel double-controlled OAd driven by the Ki67 core promoter and armed with IL-15 in glioblastoma treatment, which may help in the development of novel therapies in solid tumors.

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Section: Resultsmentioning

confidence: 98%

Efficacy of a novel double-controlled oncolytic adenovirus driven by the Ki67 core promoter and armed with IL-15 against glioblastoma cells

Zhang

Tian

et al. 2020

Cell Biosci

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“…We reported the L-R interaction including THY1 (CD90) and ITGAM/ITGB2 (Mac-1, CD11b/CD18), involved in leukocyte recruitment in response to inflammatory signals (46% of patients). The CD90 gene is a specific surface marker highly expressed in glioma-associated mesenchymal stem cells (Zhang et al, 2018). The encoded protein drives glioma progression through SRC-dependent mechanisms increasing proliferation, migration, and adhesion (Avril et al, 2017).…”

Section: Discussionmentioning

confidence: 99%

A MAP of tumor-host interactions in glioma at single cell resolution

Caruso

Garofano

D’Angelo

et al. 2019

Preprint

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Single-cell RNA sequencing is the reference technique to characterize the heterogeneity of tumor microenvironment and can be efficiently used to discover cross-talk mechanisms between immune cells and cancer cells. We present a novel method, single cell Tumor-Host Interaction tool (), to identify significantly activated ligand-receptor interactions across clusters of cells from single-cell RNA sequencing data. We apply our approach to uncover the ligand-receptor interactions in glioma using six publicly available human glioma datasets encompassing 71 patients. We provide a comprehensive map of the signalling mechanisms between malignant cells and non-malignant cells in glioma uncovering potential novel therapeutic targets.

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“…Emerging evidence suggests the pivotal role of tumor microenvironment (TME) in GBM progression, immune escape, local invasion and metastasis [ 3 ]. Generally, the TME consists of tumor cells, fibroblasts, endothelial cells, microglia, glioblastoma associated macrophages (GAMs), glioblastoma associated fibroblasts (TAFs), mesenchymal stromal cell (MSCs) and inflammatory cells, as well as cytokines and chemokines secreted by tumor and stromal cells [ 4 , 5 ]. Recently, great attention has been paid to dissect the role and the function of MSC in GBM aggressiveness.…”

Section: Introductionmentioning

confidence: 99%

“…Recently, great attention has been paid to dissect the role and the function of MSC in GBM aggressiveness. Multipotent MSCs, recruited to the tumor bulk by several soluble factors secreted by tumor cells, play complicated roles in carcinogenesis and in the modulation of tumor development [ 5 , 6 , 7 , 8 , 9 , 10 ]. When MSCs arrive at the area surrounding the tumor, they may differentiate into more mature mesenchymal cells, such as TAFs [ 11 ], macrophages [ 12 ] and endothelial cells [ 13 ].…”

Section: Introductionmentioning

confidence: 99%

“…Interestingly, the interaction of MSC with tumor cells modifies their trophic properties through the release of various cytokines such as CXCL1, CXCL2, CXCL12 or IL-6 and metalloproteinases (MMPs) that can degrade the extracellular matrix and promote tumor migration [ 15 , 16 , 17 ]. However, the link between MSC and GBM remains obscure, as well as whether MSCs play an active role in tumor promotion or suppression [ 5 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 ].…”

Section: Introductionmentioning

confidence: 99%

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High Adenosine Extracellular Levels Induce Glioblastoma Aggressive Traits Modulating the Mesenchymal Stromal Cell Secretome

Pietrobono

Giacomelli

Marchetti

et al. 2020

IJMS

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Glioblastoma is an aggressive, fast-growing brain tumor influenced by the composition of the tumor microenvironment (TME) in which mesenchymal stromal cell (MSCs) play a pivotal role. Adenosine (ADO), a purinergic signal molecule, can reach up to high micromolar concentrations in TME. The activity of specific adenosine receptor subtypes on glioma cells has been widely explored, as have the effects of MSCs on tumor progression. However, the effects of high levels of ADO on glioma aggressive traits are still unclear as is its role in cancer cells-MSC cross-talk. Herein, we first studied the role of extracellular Adenosine (ADO) on isolated human U343MG cells as a glioblastoma cellular model, finding that at high concentrations it was able to prompt the gene expression of Snail and ZEB1, which regulate the epithelial–mesenchymal transition (EMT) process, even if a complete transition was not reached. These effects were mediated by the induction of ERK1/2 phosphorylation. Additionally, ADO affected isolated bone marrow derived MSCs (BM-MSCs) by modifying the pattern of secreted inflammatory cytokines. Then, the conditioned medium (CM) of BM-MSCs stimulated with ADO and a co-culture system were used to investigate the role of extracellular ADO in GBM–MSC cross-talk. The CM promoted the increase of glioma motility and induced a partial phenotypic change of glioblastoma cells. These effects were maintained when U343MG cells and BM-MSCs were co-cultured. In conclusion, ADO may affect glioma biology directly and through the modulation of the paracrine factors released by MSCs overall promoting a more aggressive phenotype. These results point out the importance to deeply investigate the role of extracellular soluble factors in the glioma cross-talk with other cell types of the TME to better understand its pathological mechanisms.

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CD90 determined two subpopulations of glioma-associated mesenchymal stem cells with different roles in tumour progression

Cited by 32 publications

References 36 publications

Efficacy of a novel double-controlled oncolytic adenovirus driven by the Ki67 core promoter and armed with IL-15 against glioblastoma cells

Efficacy of a novel double-controlled oncolytic adenovirus driven by the Ki67 core promoter and armed with IL-15 against glioblastoma cells

A MAP of tumor-host interactions in glioma at single cell resolution

High Adenosine Extracellular Levels Induce Glioblastoma Aggressive Traits Modulating the Mesenchymal Stromal Cell Secretome

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