Objective: Glioblastoma (GBM) is a highly vascularized malignancy that relies on new vessel generation, and thus targeting angiogenesis has been a promising anti-GBM approach. ANGPTL1 is well-known for its anti-angiogenic property; nevertheless, its role in GBM is yet to be explored. Recently, the crucial role of exosomes (Exos) as intercellular communication mediators has gained prominence in GBM therapy. This work aimed to explore the role of exosomal ANGPTL1 in GBM angiogenesis and its mechanisms.
Methods: Bioinformatic analysis was performed to evaluate ANGPTL expression in GBM. Human GBM cell lines (U87 and U251) and a xenograft mouse model were employed. Exos were isolated from oe-NC- and oe-ANGPTL-transfected bone mesenchymal stem cells and identified. Cell proliferation, migration, and apoptosis were detected. Immunofluorescence, qRT-PCR, western blotting, co-immunoprecipitation, and immunohistochemistry were used to determine the molecular mechanisms underlying exosomal ANGPTL1 against GBM angiogenesis. Besides, tube generation and transmission electron microscope assays were conducted to assess GBM angiogenesis.
Results: Low ANGPTL1 expression was observed in GBM tumor tissues and cells. Functionally, e-ANGPTL-Exos inhibited GBM malignant progression and angiogenesis in vitro and in vivo. Mechanically, e-ANGPTL-Exos reduced VEGFA expression and blocked the VEGFR2/Akt/eNOS pathway in GBM cells and tumor tissues. Co-immunoprecipitation revealed a link between ANGPTL1 and VEGFA in GBM cells. Notably, oe-VEGFA abolished the suppressive functions of e-ANGPTL-Exos in GBM progression and angiogenesis and the VEGFR2/Akt/eNOS axis. The VEGFR2 inhibitor, vandetanib, eliminated the promotive effects of oe-VEGFA on GBM angiogenesis with suppressed VEGFR2/Akt/eNOS pathway.
Conclusions: Exosomal ANGPTL1 suppressed GBM angiogenesis by inhibiting the VEGFA/VEGFR2/Akt/eNOS axis.
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http://dx.doi.org/10.1016/j.jneuroim.2023.578266 | DOI Listing |
Biochim Biophys Acta Mol Basis Dis
December 2024
Department of Biochemistry, School of Basic Science, Central University of Punjab, Bathinda 151401, India. Electronic address:
Glioblastoma (GBM) is foremost the most aggressive primary brain tumor, presenting extensive therapeutic challenges due to its high invasiveness, genetic complexity, and resistance to established treatments. Despite substantial advances in surgical and chemotherapeutic interventions, the median survival rate for patients is only 14.6 months, and the prognosis remains poor.
View Article and Find Full Text PDFAsian Pac J Cancer Prev
December 2024
Guilan Road Trauma Research Center, Trauma Institute, Guilan University of Medical Sciences, Rasht, Iran.
Objective: One of the most malignant types of tumors with a remarkable ability of recurrence rate and aggressiveness is glioblastoma multiforme(GBM). Anyway, according to the restricted remedies accessible for the treatment of this serious tumor, there is no confident and stable therapeutic strategy. Notably, bioinformatics analysis can detect many effective genes in the diagnosis and treatment of GBM.
View Article and Find Full Text PDFJ Cell Mol Med
December 2024
Laboratoire d'Oncologie Moléculaire, Département de Chimie, Université du Québec à Montréal, Montreal, Quebec, Canada.
The Hippo pathway plays a tumorigenic role in highly angiogenic glioblastoma (GBM), whereas little is known about clinically relevant Hippo pathway inhibitors' ability to target adaptive mechanisms involved in GBM chemoresistance. Their molecular impact was investigated here in vitro against an alternative process to tumour angiogenesis termed vasculogenic mimicry (VM) in GBM-derived cell models. In silico analysis of the downstream Hippo signalling members YAP1, TAZ and TEAD1 transcript levels in low-grade glioblastoma (LGG) and GBM tumour tissues was performed using GEPIA.
View Article and Find Full Text PDFDiscov Oncol
December 2024
Department of Gastroenterology, Second Affiliated Hospital, Nanjing Medical University, 121 Jiangjiayuan Road, Gulou District, Nanjing, Jiangsu, China.
Background: ZBTB11 is a putative transcription factor with an N-terminal BTB domain and tandem C-terminal zinc finger motifs. Recent studies have suggested a potential role for ZBTB11 in tumorigenesis. However, the biological significance of ZBTB11 in different cancer types remains uncertain.
View Article and Find Full Text PDFProg Biophys Mol Biol
December 2024
Guilan Road Trauma Research Center, Trauma Institute, Guilan University of Medical Sciences, Rasht, Iran; Neuroscience Research Center, Trauma Institute, Guilan University of Medical Sciences, Rasht, Iran. Electronic address:
Glioblastoma (GBM) is a very deadly type of brain tumor with a poor prognosis and a short survival rate. Recent advancements in understanding GBM's molecular and genetic characteristics have led to the development of various therapeutic and diagnostic strategies. Key elements such as microRNAs, lncRNAs, exosomes, angiogenesis, and chromatin modifications are highlighted, alongside significant epigenetic alterations that impact therapy and diagnosis.
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