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Transfer of Manipulated Tumor-associated Neutrophils into Tumor-Bearing Mice to Study their Angiogenic Potential In Vivo
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Tie1 deletion inhibits tumor growth and improves angiopoietin antagonist therapy

Gabriela D'Amico, Emilia A Korhonen, Andrey Anisimov

    The Journal of Clinical Investigation
    |January 17, 2014
    PubMed

    Insights

    Targeting the Tie1 receptor in endothelial cells inhibits tumor growth and angiogenesis. Combining Tie1 blockade with angiopoietin/Tie2 inhibition offers a promising strategy for enhancing anti-angiogenic therapies.

    Area of Science:

    • Endothelial biology
    • Angiogenesis research
    • Tumor microenvironment

    Background:

    • The Tie1 receptor, while ligand-less, interacts with Tie2 for angiopoietin signaling.
    • Angiopoietin-2 (Angpt2) is implicated in tumor angiogenesis, and its blockade shows therapeutic potential.

    Purpose of the Study:

    • To investigate the role of endothelial Tie1 in tumor angiogenesis and endothelial cell survival.
    • To explore the therapeutic potential of targeting Tie1, alone or in combination with other anti-angiogenic pathways.

    Main Methods:

    • Deletion of Tie1 in adult mouse endothelium.
    • Administration of VEGF or VEGFR-2 blocking antibodies.
    • Treatment with a soluble form of Tie2 extracellular domain.
    • Analysis of postnatal retinal vasculature and Notch pathway activity.
    • Use of Angpt2 blocking antibodies in Tie1-deficient pups.

    Main Results:

    • Tie1 deletion inhibited tumor angiogenesis and growth by reducing endothelial cell survival in tumor vessels.
    • No additive effect was observed when Tie1 blockade was combined with VEGF/VEGFR-2 inhibition.
    • Combined Tie1 blockade and Angpt activity inhibition resulted in additive tumor growth inhibition.
    • Tie1 deletion affected sprouting angiogenesis and Notch pathway activity in retinal vasculature.

    Conclusions:

    • Tie1 plays a crucial role in regulating tumor angiogenesis, postnatal sprouting angiogenesis, and endothelial cell survival.
    • Targeting Tie1 in combination with Angpt/Tie2 signaling presents a potential strategy for improving anti-angiogenic therapies.

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