PDGF-mediated mesenchymal transformation renders endothelial resistance to anti-VEGF treatment in glioblastoma

@article{Liu2018PDGFmediatedMT,
  title={PDGF-mediated mesenchymal transformation renders endothelial resistance to anti-VEGF treatment in glioblastoma},
  author={Tian-run Liu and Wenjuan Ma and Haineng Xu and Menggui Huang and Duo Zhang and Zhenqiang He and L. Zhang and S. Brem and D. O’Rourke and Y. Gong and Yong-gao Mou and Zhenfeng Zhang and Yi Fan},
  journal={Nature Communications},
  year={2018},
  volume={9}
}
Angiogenesis is a hallmark of cancer. However, most malignant solid tumors exhibit robust resistance to current anti-angiogenic therapies that primarily target VEGF pathways. Here we report that endothelial-mesenchymal transformation induces glioblastoma (GBM) resistance to anti-angiogenic therapy by downregulating VEGFR-2 expression in tumor-associated endothelial cells (ECs). We show that VEGFR-2 expression is markedly reduced in human and mouse GBM ECs. Transcriptome analysis verifies… Expand
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References

SHOWING 1-10 OF 72 REFERENCES
Transdifferentiation of glioblastoma cells into vascular endothelial cells
TLDR
It is suggested that the TDEC is an important player in the resistance to anti-VEGF therapy, and hence a potential target for GBM therapy. Expand
c-Met-mediated endothelial plasticity drives aberrant vascularization and chemoresistance in glioblastoma.
TLDR
Findings illustrate a mechanism that controls aberrant tumor vascularization and suggest that targeting Endo-MT may offer selective and efficient strategies for antivascular and vessel normalization therapies in GBM, and possibly other malignant tumors. Expand
Autophagy-induced KDR/VEGFR-2 activation promotes the formation of vasculogenic mimicry by glioma stem cells
TLDR
A crucial role of autophagy is demonstrated in the formation of VM by GSCs, which may serve as a therapeutic target in drug-resistant glioma. Expand
Vascular niche IL-6 induces alternative macrophage activation in glioblastoma through HIF-2α
TLDR
It is shown, in a mouse model of glioblastoma, that endothelial cells in the TME induce macrophage M2 polarization via IL-6 and that depletion of endothelial IL-8 improves survival, and it is suggested that targeting endothelialIL-6 may offer a selective and efficient therapeutic strategy for GBM, and possibly other solid malignant tumors. Expand
Perivascular nitric oxide activates notch signaling and promotes stem-like character in PDGF-induced glioma cells.
TLDR
The potential role of nitric oxide activity in the perivascular niche (PVN) using a genetic engineered mouse model of PDGF-induced gliomas and the NO/cGMP/PKG pathway's promotion of stem cell-like character in the tumor PVN may identify therapeutic targets for this subset ofgliomas. Expand
Benefits of targeting both pericytes and endothelial cells in the tumor vasculature with kinase inhibitors.
TLDR
Combinatorial targeting of receptor tyrosine kinases shows promise for treating multiple stages in tumorigenesis, most notably the often-intractable late-stage solid tumor. Expand
Inhibition of vascular endothelial growth factor-induced angiogenesis suppresses tumour growth in vivo
TLDR
It is demonstrated that inhibition of the action of an angiogenic factor spontaneously produced by tumour cells may suppress tumour growth in vivo. Expand
Angiocrine factors deployed by tumor vascular niche induce B cell lymphoma invasiveness and chemoresistance.
TLDR
It is shown that FGF4 produced by B cell lymphoma cells (LCs) through activating FGFR1 upregulates the Notch ligand Jagged1 (Jag1) on neighboring ECs. Expand
Profilin-1 Phosphorylation Directs Angiocrine Expression and Glioblastoma Progression through HIF-1α Accumulation
TLDR
A feedforward mechanism in which endothelial cells, in response to tumour-derived mediators, release angiocrines driving aberrant vascularization and glioblastoma multiforme (GBM) progression through a hypoxia-independent induction of hypoxIA-inducible factor (HIF)-1α is identified. Expand
Ephrin-B2 controls VEGF-induced angiogenesis and lymphangiogenesis
TLDR
It is shown with genetic experiments in mouse and zebrafish that ephrin-B2, a transmembrane ligand for Eph receptor tyrosine kinases, promotes sprouting behaviour and motility in the angiogenic endothelium, and shows that full VEGFR3 signalling is coupled to receptor internalization. Expand
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2
3
4
5
...