Notch in Pathological Angiogenesis and Lymphangiogenesis
Annual summary rept. 1 May 2010-30 Apr 2013
COLUMBIA UNIV NEW YORK
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The purpose of this study was to determine the role of Notch in lymphatic endothelial cell LEC behavior and to determine the effects on tumor vasculature upon Notch inhibition. We hypothesized that disrupting Notch activity may interfere with tumor lymphangiogenesis by disrupting expression and activity of EC genes. To that end, we have created a treatment agent known as Notch1 decoy hN1DFc. Activation or inactivation of Notch changes the gene profile of LEC and changes their in vitro behavior. An orthotopic model of human breast cancer was established. These tumors are rich in Notch-positive vasculature and metastasize to the lungs andor lymph nodes. Tumor studies showed that hN1DFc did not significantly inhibit tumor growth, vascularization, or metastasis in this model. However, this does not exclude the possibility that hN1DFc could be an effective tumor growthvascularizationmetastasis inhibitor in other tumor models. Therefore, further investigation will be necessary to determine the potential use of Notch inhibitors in tumors.
- Anatomy and Physiology
- Medicine and Medical Research