ArticleNeuro-oncology2021
Nestin+/CD31+ cells in the hypoxic perivascular niche regulate glioblastoma chemoresistance by upregulating JAG1 and DLL4.
Article in Neuro-oncology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 29 citations in OpenAlex.
- Human Blood-Brain Tumor Barrier on a Chip to Investigate Personalized Treatment for Glioblastoma Patients.Small (Weinheim an der Bergstrasse, Germany) · 2026Article
- Understanding Glioblastoma Dynamics Using 3D Organoids and Engineered Extracellular Matrix.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Glioblastoma Stem Cells and Tumour Microenvironment: Interactions Across Hypoxia, Vasculature and Immune Modulation.International journal of molecular sciences · 2026Review
- Review
- Nested ecosystems theory for conceptualizing brain tumors.Disease models & mechanisms · 2026Review
- Angiogenesis and Resistance Mechanisms in Glioblastoma: Targeting Alternative Vascularization Pathways to Overcome Therapy Resistance.Current pharmaceutical design · 2026Review
- Glioblastoma insights: Focus on crosstalk with the suppressive tumor microenvironment and advanced therapeutic strategies.Medicine · 2025Review
- Understanding proneural-mesenchymal transition using patient-derived glioma stem-like cell (GSC) organoids and engineered extracellular matrix.bioRxiv : the preprint server for biology · 2025Article
- Endothelial transdifferentiation of glioma stem cells: a literature review.Acta neuropathologica communications · 2025Review
- HES1 in cancer: a key player in tumorigenesis and its prognostic significance.Molecular genetics and genomics : MGG · 2025Review
- Nestin in multiple myeloma: emerging insights into a potential therapeutic target.Frontiers in oncology · 2025Review
- Exosomal circZNF800 Derived from Glioma Stem-like Cells Regulates Glioblastoma Tumorigenicity via the PIEZO1/Akt Axis.Molecular neurobiology · 2024Article
- A novel risk signature for predicting brain metastasis in patients with lung adenocarcinoma.Neuro-oncology · 2023Article
- Development and validation of an immune infiltration/tumor proliferation-related Notch3 nomogram for predicting survival in patients with primary glioblastoma.Frontiers in genetics · 2023Article
- Glioblastoma-Specific Strategies of Vascularization: Implications in Anti-Angiogenic Therapy Resistance.Journal of personalized medicine · 2022Review
- Hypoxia-induced polypoid giant cancer cells in glioma promote the transformation of tumor-associated macrophages to a tumor-supportive phenotype.CNS neuroscience & therapeutics · 2022Article
- To Explore the Stem Cells Homing to GBM: The Rise to the Occasion.Biomedicines · 2022Review
- Article
- The Role and Mechanism of the Vascular Endothelial Niche in Diseases: A Review.Frontiers in physiology · 2022Review
- Hypoxia associated lncRNA HYPAL promotes proliferation of gastric cancer as ceRNA by sponging miR-431-5p to upregulate CDK14.Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association · 2022Article
Corrections and comments
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Authors and funding
10 authors at 6 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundFailure of glioblastoma (GBM) therapy is often ascribed to different types of glioblastoma stem-like cell (GSLC) niche; in particular, a hypoxic perivascular niche (HPVN) is involved in GBM progression. However, the cells responsible for HPVNs remain unclear.
methodsImmunostaining was performed to determine the cells involved in HPVNs. A hypoxic chamber and 3-dimensional (3D) microfluidic chips were designed to simulate a HPVN based on the pathological features of GBM. The phenotype of GSLCs was evaluated by fluorescence scanning in real time and proliferation and apoptotic assays. The expression of JAG1, DLL4, and Hes1 was determined by immunostaining, ELISA, Western blotting, and quantitative PCR. Their clinical prognostic significance in GBM HPVNs and total tumor tissues were verified by clinical data and The Cancer Genome Atlas databases.
resultsNestin+/CD31+ cells and pericytes constitute the major part of microvessels in the HPVN, and the high ratio of nestin+/CD31+ cells rather than pericytes are responsible for the poor prognosis of GBM. A more real HPVN was simulated by a hypoxic coculture system in vitro, which consisted of 3D microfluidic chips and a hypoxic chamber. Nestin+/CD31+ cells in the HPVN were derived from GSLC transdifferentiation and promoted GSLC chemoresistance by providing more JAG1 and DLL4 to induce downstream Hes1 overexpression. Poor GBM prognosis correlated with Hes1 expression of tumor cells in the GBM HPVN, and not with total Hes1 expression in GBM tissues.
conclusionsThese results highlight the critical role of nestin+/CD31+ cells in HPVNs that acts in GBM chemoresistance and reveal the distinctive prognostic value of these molecular markers in HPVNs.
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