Notch in Pathological Angiogenesis and Lymphangiogenesis
Annual summary rept. 1 May 2010-30 Apr 2011
COLUMBIA UNIV NEW YORK
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The purpose of this study was to determine the role of Notch signaling in lymphatic endothelial cell LEC behavior and to determine the effects on tumor vasculature upon Notch inhibition. We hypothesized that inhibiting Notch activity may disrupt tumor lymphangiogenesis by changing expression and activity of EC genes. To that end, we have created a treatment agent known as Notch1 decoy hN1DFc. Activation of Notch changes the gene profile of LEC and changes their in vitro behavior. An orthotopic model of human breast cancer was established. Pilot studies show that expression by these tumors of a mutant VEGF-C induces tumor lymphangiogenesis and lymph node metastasis. These tumors are rich in Notch-positive vasculature, making this a good model for future studies of Notch inhibition on tumor vasculature.
- Medicine and Medical Research