Notch in Pathological Angiogenesis and Lymphangiogenesis

Abstract

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 (lymph)angiogenesis 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 and/or 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 growth/vascularization/metastasis inhibitor in other tumor models. Therefore, further investigation will be necessary to determine the potential use of Notch inhibitors in tumors.

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Document Details

Document Type
Technical Report
Publication Date
May 01, 2013
Accession Number
ADA581029

Entities

People

  • Minji Kim

Organizations

  • Columbia University

Tags

DTIC Thesaurus Topics

  • Angiogenesis
  • Biomedical Research
  • Blood
  • Blood Vessels
  • Breast Cancer
  • Cancer
  • Carcinoma
  • Cell Line
  • Cells
  • Cellular Structures
  • Department Of Defense
  • Endothelial Cells
  • Inhibition
  • Lymph Nodes
  • Lymphatic System
  • Lymphatic Vessels
  • Neoplasms

Fields of Study

  • Biology
  • Medicine

Readers

  • Immunology and Pathology
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  • Oncology and Biomarker-Based Cancer Detection.