Angiopoietin-2 decreases vascular endothelial growth factor expression by modulating HIF-1α levels in gliomas

Lee, O. H.; Xu, Jing; Fueyo, Juan; Alonso, Marta M.; Liu, D.; Martı́n, Vanesa; Jiang, Hong; Piao, Yuji; Liu, T. J.; Gomez-Manzano, Candelaria

doi:10.1038/sj.onc.1210731

Cited by 17 publications

(17 citation statements)

References 17 publications

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“…15 Angiogenesis is dependent on a perfectly coordinated balance between endogenous-positive and -negative regulatory factors, including VEGF and the Ang's. 16 In a previous study, we showed that VEGF and Ang-1 levels were significantly higher and Ang-2 levels were significantly lower in NPs than in inferior turbinates. 12 Based on these observations, we suggested that VEGF and Ang-1 act as positive regulators of angiogenesis in NPs, and Ang-2 is an inhibitor.…”

Section: Discussionmentioning

confidence: 96%

Effects of Methotrexate on Vascular Endothelial Growth Factor, Angiopoietin 1, and Angiopoietin 2 in Nasal Polyps

Park

Kim

Yang

et al. 2011

Am J Rhinol�Allergy

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Section: Discussionmentioning

confidence: 96%

Effects of Methotrexate on Vascular Endothelial Growth Factor, Angiopoietin 1, and Angiopoietin 2 in Nasal Polyps

Park

Kim

Yang

et al. 2011

Am J Rhinol�Allergy

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“…Ang2 regulated VEGF expression at the transcriptional level in relation to a decrease in hypoxia-inducible factor (HIF)-1α expression and HIF-DNA–binding activity. Tie2 silencing by small interfering RNA (siRNA) rescued the Ang2-mediated down-modulation of VEGF, suggesting an essential role for Tie2 in this regulatory loop [28]. …”

Section: Ang2 Signaling and Modulationmentioning

confidence: 99%

“…In rats, injection of this anti-Ang2 antibody inhibited VEGF-induced corneal angiogenesis in the eye. Lastly, Cao et al [18•] and Lee et al [28] demonstrated that Ang2 also may be considered an inhibitor for suppression of tumor angiogenesis because systemic expression or overexpression of Ang2 attenuated VEGF expression in glioma cells expressing Ang2, impaired pericyte coverage of the tumor vasculature, inhibited EC proliferation, and induced EC apoptosis, resulting in a massive regression of tumor vasculature and tumor growth.…”

Section: Therapeutic Implications For Ang2mentioning

confidence: 99%

Angiopoietin-2: Development of inhibitors for cancer therapy

Hu¹,

Cheng

2009

Curr Oncol Rep

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Angiopoietin-2 (Ang2) is a member of the Ang family, which plays an important role in angiogenesis during the development and growth of human cancers. Ang2’s role in angiogenesis generally is considered as an antagonist for Ang1, inhibiting Ang1-promoted Tie2 signaling, which is critical for blood vessel maturation and stabilization. Ang2 modulates angiogenesis in a cooperative manner with another important angiogenic factor, vascular endothelial growth factor A. Genetic studies have revealed that Ang2 also is critical in lymphangiogenesis during development. However, new evidence suggests more complicated roles for Ang2 in angiogenesis in physiologic processes and invasive phenotypes of cancer cells during progression of human cancers. This article discusses recent studies of Ang2 in angiogenesis and the implication of Ang2 as a therapeutic target as well as a potential inhibitor for antiangiogenesis treatment for cancer patients.

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“…Tie2 is a good candidate for the modulation of the tumor chemoresistance because its activation by Ang1 renders hematopoietic stem cells resistant to myelosuppressive stress, and Tie2 + cells in the niche were ultimately responsible for repopulating the bone marrow (Arai et al , 2004). Our group was the first to report aberrant Tie2 expression in neoplastic glial cells in more than 50% of malignant brain tumors and showed the existence of a Tie2-mediated functional signaling in these tumors (Lee et al , 2006, 2008). …”

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confidence: 98%

Tie2-mediated multidrug resistance in malignant gliomas is associated with upregulation of ABC transporters

Martı́n

Kumar

et al. 2009

Oncogene

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Resistance and relapse are still primary causes that result in poor effectiveness of chemotherapy in malignant gliomas. Therefore, development of new therapeutic strategies requires the identification of key molecular pathways regulating chemoresistance. We previously found that abnormal high expression of the Tie2 receptor in gliomas was associated with tumor malignancy. Here, we studied the role of Tie2 activation in drug resistance by testing the cytotoxicity of several chemotherapeutic drugs in a panel of human glioma cell lines and brain tumor stem cells and found that Tie2 activation was significantly related to chemoresistance. The essential role of Tie2 in this phenotype was illustrated by silencing Tie2 using specific siRNA, and the subsequent abrogation of the angiopoietin 1 (Ang1)-mediated chemoresistance. Using quantitative real-time PCR and functional drug efflux studies, we observed that Tie2 activation resulted in increased expression of ATP-binding cassette (ABC) transporters. Consistent with these results, downmodulation of ABCG2 or ABCC2 resulted in the inability of Tie2 activation to induce a chemoresistant phenotype. Our results indicate that Tie2 activation may be important in modifying the evolution of gliomas during conventional chemotherapy regimens, and open new avenues for the search of more effective therapies to avoid the inevitable brain tumor recurrence.

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Angiopoietin-2 decreases vascular endothelial growth factor expression by modulating HIF-1α levels in gliomas

Cited by 17 publications

References 17 publications

Effects of Methotrexate on Vascular Endothelial Growth Factor, Angiopoietin 1, and Angiopoietin 2 in Nasal Polyps

Effects of Methotrexate on Vascular Endothelial Growth Factor, Angiopoietin 1, and Angiopoietin 2 in Nasal Polyps

Angiopoietin-2: Development of inhibitors for cancer therapy

Tie2-mediated multidrug resistance in malignant gliomas is associated with upregulation of ABC transporters

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