ArticleThe Journal of biological chemistry2012
Glioblastoma-derived tumor cells induce vasculogenic mimicry through Flk-1 protein activation.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 86 papers.
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Who cites it
86 citing papers in PubMed, 142 citations in OpenAlex.
- Research progress on vasculogenic mimicry in colorectal cancer: mechanisms and therapeutic.Cell division · 2026Review
- The Interaction Between Vasculogenic Mimicry and the Immune System: Mechanistic Insights and Dual Exploration in Cancer Therapy.Cell proliferation · 2025Review
- Exosomes in glioma: mechanistic insights on biological, therapeutic, and diagnostic perspective.Therapeutic delivery · 2025Review
- Claudin and transmembrane receptor protein gene expressions are reversely correlated in peritumoral brain edema.Cancer medicine · 2024Article
- Understanding the Role of Endothelial Cells in Glioblastoma: Mechanisms and Novel Treatments.International journal of molecular sciences · 2024Review
- Preclinical Models and Technologies in Glioblastoma Research: Evolution, Current State, and Future Avenues.International journal of molecular sciences · 2023Review
- Article
- Double Immunohistochemical Staining on Formalin-Fixed Paraffin-Embedded Tissue Samples to Study Vascular Co-option.Methods in molecular biology (Clifton, N.J.) · 2023Article
- Differential P-Glycoprotein/CD31 Expression as Markers of Vascular Co-Option in Primary Central Nervous System Tumors.Diagnostics (Basel, Switzerland) · 2022Article
- Glioblastoma-Specific Strategies of Vascularization: Implications in Anti-Angiogenic Therapy Resistance.Journal of personalized medicine · 2022Review
- Propranolol blocks osteosarcoma cell cycle progression, inhibits angiogenesis and slows xenograft growth in combination with cisplatin-based chemotherapy.Scientific reports · 2022Article
- Nanotherapeutic treatment of the invasive glioblastoma tumor microenvironment.Advanced drug delivery reviews · 2022Review
- Molecular and Circulating Biomarkers in Patients with Glioblastoma.International journal of molecular sciences · 2022Review
- Paradoxical role of β8 integrin on angiogenesis and vasculogenic mimicry in glioblastoma.Cell death & disease · 2022Article
- Impact of Regorafenib on Endothelial Transdifferentiation of Glioblastoma Stem-like Cells.Cancers · 2022Article
- Vasculogenic mimicry structures in melanoma support the recruitment of monocytes.Oncoimmunology · 2022Article
- Vasculogenic Mimicry-An Overview.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Cyr61 from adipose-derived stem cells promotes colorectal cancer metastasis and vasculogenic mimicry formation via integrin αMolecular oncology · 2021Article
- Tumor Vessels Fuel the Fire in Glioblastoma.International journal of molecular sciences · 2021Review
- Article
26 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
Glioblastoma (GBM) is extremely aggressive and essentially incurable. Its malignancy is characterized by vigorous microvascular proliferations. Recent evidence has shown that tumor cells display the ability to drive blood-perfused vasculogenic mimicry (VM), an alternative microvascular circulation independent of endothelial cell angiogenesis. However, molecular mechanisms underlying this vascular pathogenesis are poorly understood. Here, we found that vascular channels of VM in GBM were composed of mural-like tumor cells that strongly express VEGF receptor 2 (Flk-1). To explore a potential role of Flk-1 in the vasculogenesis, we investigated two glioblastoma cell lines U87 and GSDC, both of which express Flk-1 and exhibit a vascular phenotype on Matrigel. Treatment of both cell lines with either Flk-1 gene knockdown or Flk-1 kinase inhibitor SU1498 abrogated Flk-1 activity and impaired vascular function. Furthermore, inhibition of Flk-1 activity suppressed intracellular signaling cascades, including focal adhesion kinase and mitogen-activated protein kinase ERK1/2. In contrast, blockade of VEGF activity by the neutralizing antibody Bevacizumab failed to recapitulate the impact of SU1498, suggesting that Flk-1-mediated VM is independent of VEGF. Xenotransplantation of SCID/Beige mice with U87 cells and GSDCs gave rise to tumors harboring robust mural cell-associated vascular channels. Flk-1 shRNA restrained VM in tumors and subsequently inhibited tumor development. Collectively, all the data demonstrate a central role of Flk-1 in the formation of VM in GBM. This study has shed light on molecular mechanisms mediating tumor aggressiveness and also provided a therapeutic target for patient treatment.
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