ArticleJournal of Cancer2016
Vasculogenic Mimicry in Prostate Cancer: The Roles of EphA2 and PI3K.
Article in Journal of Cancer, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers, 1 of them a synthesis that pooled it.
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Who cites it
43 citing papers in PubMed, 1 synthesis or guideline pooled it, 78 citations in OpenAlex.
- Correlation Between Tumor Vasculogenic Mimicry and Poor Prognosis of Human Digestive Cancer Patients: A Systematic Review and Meta-Analysis.Pathology oncology research : POR · 2019Pooled it
- EphA2 as an oncogenic driver: roles and mechanisms of action in cancer.Molecular biology reports · 2026Review
- Knockout of PAK1 and PAK4 supresses tumour growth associated with vasculogenic mimicry inhibition through EphA2-VE-cadherin-MCAM pathway.Cell communication and signaling : CCS · 2026Article
- Pomegranate root extract possesses anti-metastatic potential by suppressing invasiveness and vasculogenic mimicry capability of cancer cells.Biochemistry and biophysics reports · 2025Article
- Dihydroartemisinin inhibits EphA2/PI3K/Akt pathway-mediated malignant behaviors and vasculogenic mimicry in glioma stem cells.Heliyon · 2025Article
- The Blood-prostate Barrier: An Obstacle to Drug Delivery into the Prostate.Current drug delivery · 2025Review
- The deubiquitinase USP7 and E3 ligase TRIM21 regulate vasculogenic mimicry and malignant progression of RMS by balancing SNAI2 homeostasis.Journal of experimental & clinical cancer research : CR · 2024Article
- Article
- Prostate Cancer Microvascular Routes: Exploration and Measurement Strategies.Life (Basel, Switzerland) · 2023Review
- Therapeutic potential of vasculogenic mimicry in urological tumors.Frontiers in oncology · 2023Review
- Start Early and See Inflammatory; Late, Nothing Save RAVE: How to Appreciate Radiation Proctitis as a Continuum.Gastro hep advances · 2023Article
- Vasculogenic mimicry score identifies the prognosis and immune landscape of lung adenocarcinoma.Frontiers in genetics · 2023Article
- Physicochemical aspects of the tumour microenvironment as drivers of vasculogenic mimicry.Cancer metastasis reviews · 2022Review
- Resveratrol suppresses serum-induced vasculogenic mimicry through impairing the EphA2/twist-VE-cadherin/AKT pathway in human prostate cancer PC-3 cells.Scientific reports · 2022Article
- Article
- Accuracy of fractal analysis and PI-RADS assessment of prostate magnetic resonance imaging for prediction of cancer grade groups: a clinical validation study.European radiology · 2022Article
- Sp1 Plays a Key Role in Vasculogenic Mimicry of Human Prostate Cancer Cells.International journal of molecular sciences · 2022Article
- Histochemical Staining of Vasculogenic Mimicry.Methods in molecular biology (Clifton, N.J.) · 2022Review
- Development of EphA2 siRNA-loaded lipid nanoparticles and combination with a small-molecule histone demethylase inhibitor in prostate cancer cells and tumor spheroids.Journal of nanobiotechnology · 2021Article
- Extracellular vesicle mimics made from iPS cell-derived mesenchymal stem cells improve the treatment of metastatic prostate cancer.Stem cell research & therapy · 2021Article
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundAggressive tumor cells can form perfusable networks that mimic normal vasculature and enhance tumor growth and metastasis. A number of molecular players have been implicated in such vasculogenic mimicry, among them the receptor tyrosine kinase EphA2, which is aberrantly expressed in aggressive tumors. Here we study the role and regulation of EphA2 in vasculogenic mimicry in prostate cancer where this phenomenon is still poorly understood.
methodsVasculogenic mimicry was characterized by tubules whose cellular lining was negative for the endothelial cell marker CD34 but positive for periodic acid-Schiff staining, and/or contained red blood cells. Vasculogenic mimicry was assessed in 92 clinical samples of prostate cancer and analyzed in more detail in three prostate cancer cell lines kept in three-dimensional culture. Tissue samples and cell lines were also assessed for total and phosphorylated levels of EphA2 and its potential regulator, Phosphoinositide 3-Kinase (PI3K). In addition, the role of EphA2 in vasculogenic mimicry and in cell migration and invasion were investigated by manipulating the levels of EphA2 through specific siRNAs. Furthermore, the role of PI3K in vasculogenic mimicry and in regulating EphA2 was tested by application of an inhibitor, LY294002.
resultsImmunohistochemistry of prostate cancers showed a significant correlation between vasculogenic mimicry and high expression levels of EphA2, high Gleason scores, advanced TNM stage, and the presence of lymph node and distant metastases. Likewise, two prostate cancer cell lines (PC3 and DU-145) formed vasculogenic networks on Matrigel and expressed high EphA2 levels, while one line (LNCaP) showed no vasculogenic networks and lower EphA2 levels. Specific silencing of EphA2 in PC3 and DU-145 cells decreased vasculogenic mimicry as well as cell migration and invasion. Furthermore, high expression levels of PI3K and EphA2 phosphorylation at Ser897 significantly correlated with the presence of vasculogenic mimicry and in vitro inhibition of PI3K by LY294002 disrupted vasculogenic mimicry, potentially through a reduction of EphA2 phosphorylation at Ser897.
conclusionsThe expression levels of PI3K and EphA2 are positively correlated with vasculogenic mimicry both in vivo and in vitro. Moreover, phosphorylation levels of EphA2 regulated by PI3K are also significantly associated with vasculogenic mimicry in vivo. Based on its functional implication in vasculogenic mimicry in vitro, EphA2 signaling may be a potential therapeutic target in advanced prostate cancer.
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