Multi-targeting Peptide-Functionalized Nanoparticles Recognized Vasculogenic Mimicry, Tumor Neovasculature, and Glioma Cells for Enhanced Anti-glioma Therapy

2015 ◽  
Vol 7 (50) ◽  
pp. 27885-27899 ◽  
Author(s):  
Xingye Feng ◽  
Jianhui Yao ◽  
Xiaoling Gao ◽  
Yixian Jing ◽  
Ting Kang ◽  
...  
Keyword(s):  
Vasculogenic Mimicry ◽  
Glioma Cells ◽  
Functionalized Nanoparticles ◽  
Tumor Neovasculature ◽  
Targeting Peptide

scholarly journals Theranostic Design of Angiopep-2 Conjugated Hyaluronic Acid Nanoparticles (Thera-ANG-cHANPs) for Dual Targeting and Boosted Imaging of Glioma Cells

Cancers ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 503
Author(s):  
Angela Costagliola di Polidoro ◽  
Giorgia Zambito ◽  
Joost Haeck ◽  
Laura Mezzanotte ◽  
Martine Lamfers ◽  
...  
Keyword(s):  
Hyaluronic Acid ◽  
Clinical Care ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Glioma Cells ◽  
Drug Molecules ◽  
Dual Targeting ◽  
Density Lipoprotein Receptor ◽  
Targeting Peptide

Glioblastoma multiforme (GBM) has a mean survival of only 15 months. Tumour heterogeneity and blood-brain barrier (BBB) mainly hinder the transport of active agents, leading to late diagnosis, ineffective therapy and inaccurate follow-up. The use of hydrogel nanoparticles, particularly hyaluronic acid as naturally occurring polymer of the extracellular matrix (ECM), has great potential in improving the transport of drug molecules and, furthermore, in facilitatating the early diagnosis by the effect of hydrodenticity enabling the T1 boosting of Gadolinium chelates for MRI. Here, crosslinked hyaluronic acid nanoparticles encapsulating gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA) and the chemotherapeutic agent irinotecan (Thera-cHANPs) are proposed as theranostic nanovectors, with improved MRI capacities. Irinotecan was selected since currently repurposed as an alternative compound to the poorly effective temozolomide (TMZ), generally approved as the gold standard in GBM clinical care. Also, active crossing and targeting are achieved by theranostic cHANPs decorated with angiopep-2 (Thera-ANG-cHANPs), a dual-targeting peptide interacting with low density lipoprotein receptor related protein-1(LRP-1) receptors overexpressed by both endothelial cells of the BBB and glioma cells. Results showed preserving the hydrodenticity effect in the advanced formulation and internalization by the active peptide-mediated uptake of Thera-cHANPs in U87 and GS-102 cells. Moreover, Thera-ANG-cHANPs proved to reduce ironotecan time response, showing a significant cytotoxic effect in 24 h instead of 48 h.

scholarly journals SUMOylation of PUM2 promotes the vasculogenic mimicry of glioma cells via regulating CEBPD

2020 ◽  
Vol 10 (5) ◽  
Author(s):  
Di Wang ◽  
Xuelei Ruan ◽  
Xiaobai Liu ◽  
Yixue Xue ◽  
Lianqi Shao ◽  
...  
Keyword(s):  
Vasculogenic Mimicry ◽  
Glioma Cells

scholarly journals M2-like tumor-associated macrophages drive vasculogenic mimicry through amplification of IL-6 expression in glioma cells

Oncotarget ◽  
2016 ◽  
Vol 8 (1) ◽  
pp. 819-832 ◽  
Author(s):  
Lin Zhang ◽  
Yangyang Xu ◽  
Jintang Sun ◽  
Weiliang Chen ◽  
Lei Zhao ◽  
...  
Keyword(s):  
Vasculogenic Mimicry ◽  
Glioma Cells ◽  
Tumor Associated Macrophages

scholarly journals MicroRNA-Let-7f reduces the vasculogenic mimicry of human glioma cells by regulating periostin-dependent migration

2016 ◽  
Vol 35 (3) ◽  
pp. 1771-1777 ◽  
Author(s):  
HAO XUE ◽  
XIAO GAO ◽  
SHUGANG XU ◽  
JINSEN ZHANG ◽  
XING GUO ◽  
...  
Keyword(s):  
Vasculogenic Mimicry ◽  
Glioma Cells ◽  
Human Glioma ◽  
Human Glioma Cells

scholarly journals HNRNPD interacts with ZHX2 regulating the vasculogenic mimicry formation of glioma cells via linc00707/miR-651-3p/SP2 axis

2021 ◽  
Vol 12 (2) ◽  
Author(s):  
Sifei Yu ◽  
Xuelei Ruan ◽  
Xiaobai Liu ◽  
Fangfang Zhang ◽  
Di Wang ◽  
...  
Keyword(s):  
Rna Binding ◽  
Rna Binding Proteins ◽  
Vasculogenic Mimicry ◽  
Glioma Cells ◽  
Specific Protein ◽  
The Cancer Genome Atlas ◽  
Migration And Invasion ◽  
Promoter Regions ◽  
The Stability ◽  
Nuclear Ribonucleoprotein

AbstractStudies have found that RNA-binding proteins (RBPs) are dysfunctional and play a significant regulatory role in the development of glioma. Based on The Cancer Genome Atlas database and the previous studies, we selected heterogeneous nuclear ribonucleoprotein (HNRNPD) as the research candidate and sought its downstream targeted genes. In the present study, HNRNPD, linc00707, and specific protein 2 (SP2) were highly expressed, while zinc fingers and homeboxes 2 (ZHX2) and miR-651-3p were remarkedly downregulated in glioma tissues and cells. HNRNPD, linc00707, and SP2 knockdown or ZHX2 and miR-651-3p overexpression suppressed glioma cells proliferation, migration, and invasion and vasculogenic mimicry (VM) formation. Knockdown of HNRNPD increased the stability of ZHX2 mRNA. ZHX2 bound to the promoter region of linc00707 and negatively regulate its expression. Linc00707 could bind with miR-651-3p, while miR-651-3p bound to the 3′ untranslated region (3′UTR) of SP2 mRNA to negatively regulate its expression. The transcription factor SP2 directly bound to the promoter regions of the VM formation-related proteins MMP2, MMP9, and VE-cadherin, playing a role in promoting transcription in order to regulate the VM formation ability of glioma cells.

scholarly journals Biosynthetic circ-PLEKHA5 stabilized by SRSF7 promotes the vasculogenic mimicry of glioblastoma cells by encoding a novel protein 622aa

2020 ◽  
Author(s):  
Rui Su ◽  
Xiaobai Liu ◽  
Hao Teng ◽  
Xuelei Ruan ◽  
Di Wang ◽  
...  
Keyword(s):  
Vasculogenic Mimicry ◽  
Glioma Cells ◽  
Immunofluorescence Assay ◽  
Luciferase Assay ◽  
Migration And Invasion ◽  
Glioblastoma Cells ◽  
Associated Proteins ◽  
Novel Strategy ◽  
Novel Protein

Abstract Background: Increasing studies have been demonstrated that circRNAs play vital regulatory roles in the biological behaviors of glioblastoma cells, and increasing circRNAs are found to have the capacity of encoding small peptides, which are involved in the regulatory process.Methods: Western blot and qRT-PCR were conducted to confirm the expression of SRSF7 and circ-PLEKHA5 respectively. RNase R digestion assay and fluorescence in situ hybridization assays were conducted to evaluate the existence and cellular location of circ-PLEKHA5. RIP assay was used to access the relationship between SRSF7 and circ-PLEKHA5. Dual-luciferase assay and FLAG tag assays were performed to test the coding capability of circ-PLEKHA5. Immunofluorescence assay was conducted to evaluate the location of circ-PLEKHA5-622aa. CCK-8, vasculogenic mimicry (VM) formation and transwell assays were used to evaluate the roles of SRSF7, circ-PLEKHA5, circ-PLEKHA5-622aa on proliferation, VM formation, migration and invasion. Nude mice xenograft studys with PAS-CD34 staining were used to clarify the functional roles of SRSF7 and circ-PLEKHA5 on VM formation in vivo.Results: SRSF7 was up-regulated in glioma, and promoted the proliferation, migration, invasion, VM formation and the expression of VM-associated proteins of glioma cells by increasing the expression of circ-PLEKHA5. Circ-PLEKHA5 was mainly localized in cytoplasm and promoted the proliferation, migration, invasion, VM formation and the expression of VM-associated proteins of glioma cells by encoding a novel protein circ-PLEKHA5-622aa. The application of SRSF7 and circ-PLEKHA5 inhibitor significantly suppressed the tumor growth and VM formation in vivo.Conclusions: This study first demonstrated the coding ability of circ-PLEKHA5, and identified the regulatory roles of SRSF7/circ-PLEKHA5/circ-PLEKHA5-622aa pathway in VM formation of glioblastoma cells. Our findings might provide a novel strategy for glioma treatment.

scholarly journals Tenascin-c mediated vasculogenic mimicry formation via regulation of MMP2/MMP9 in glioma

2019 ◽  
Vol 10 (12) ◽  
Author(s):  
Hai-ping Cai ◽  
Jing Wang ◽  
Shao-yan Xi ◽  
Xiang-rong Ni ◽  
Yin-sheng Chen ◽  
...  
Keyword(s):  
Matrix Metalloproteinase ◽  
Vasculogenic Mimicry ◽  
Glioma Cells ◽  
Matrix Metalloproteinase 2 ◽  
Potential Therapeutic Target ◽  
Akt Phosphorylation ◽  
Tenascin C ◽  
And Migration

AbstractVasculogenic mimicry (VM), the formation of vessel-like structures by highly invasive tumor cells, has been considered one of several mechanisms responsible for the failure of anti-angiogenesis therapy in glioma patients. Therefore, inhibiting VM formation might be an effective therapeutic method to antagonize the angiogenesis resistance. This study aimed to show that an extracellular protein called Tenascin-c (TNC) is involved in VM formation and that TNC knockdown inhibits VM in glioma. TNC was upregulated with an increase in glioma grade. TNC and VM formation are potential independent predictors of survival of glioma patients. TNC upregulation was correlated with VM formation, and exogenous TNC stimulated VM formation. Furthermore, TNC knockdown significantly suppressed VM formation and proliferation in glioma cells in vitro and in vivo, with a reduction in cellular invasiveness and migration. Mechanistically, TNC knockdown decreased Akt phosphorylation at Ser473 and Thr308 and subsequently downregulated matrix metalloproteinase 2 and 9, both of which are important proteins associated with VM formation and migration. Our results indicate that TNC plays an important role in VM formation in glioma, suggesting that TNC is a potential therapeutic target for anti-angiogenesis therapy for glioma.

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