Driving Neurofibroma Formation in Mice
Abstract
Benign peripheral nerve tumors called neurofibromas are a major burden for patients with neurofibromatosis type 1 (NF1). No drug therapy is currently available for neurofibromas. Some Schwann cells in neurofibromas aberrantly express the epidermal growth factor receptor, making EGFR a possible therapeutic target. To test this, we used a novel transgenic mouse line in which the human EGFR is expressed in Schwann cells and in which nerve ultrastructure shows features of neurofibroma formation including Schwann cell hyperplasia, nerve hypertrophy, collagen deposition, and axon-glial disruption. We used the mAb Cetuximab (IMC-C225) to block human EGFR function in these mice and assessed nerve hypertrophy, mast cell accumulation, collagen deposition and axon-glial interactions normal at 3 months age. Hot plate sensory tests and electron microscopy confirmed histology data. To ascertain whether EGFR is necessary for malignant tumor formation in NF1, NPCis mice were mated to an EGFR hypomorph. The results of these studies suggest that EGFR acquisition is a key driving force for tumorigenesis in NF1.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2006
- Accession Number
- ADA462142
Entities
People
- Nancy Ratner