| First Author | Wu J | Year | 2006 |
| Journal | Am J Pathol | Volume | 168 |
| Issue | 5 | Pages | 1686-96 |
| PubMed ID | 16651634 | Mgi Jnum | J:108591 |
| Mgi Id | MGI:3624379 | Doi | 10.2353/ajpath.2006.050859 |
| Citation | Wu J, et al. (2006) Perinatal epidermal growth factor receptor blockade prevents peripheral nerve disruption in a mouse model reminiscent of benign world health organization grade I neurofibroma. Am J Pathol 168(5):1686-96 |
| abstractText | Benign peripheral nerve tumors called neurofibromas are a major source of morbidity for patients with neurofibromatosis type 1. Some neurofibroma Schwann cells aberrantly express the epidermal growth factor receptor (EGFR). In a mouse model in which the CNPase promoter drives expression of human EGFR in Schwann cells, nerves develop hypertrophy, mast cell accumulation, collagen deposition, disruption of axon-glial interactions, characteristics of neurofibroma and are hypoalgesic. Administration of the EGFR antagonist cetuximab (IMC-C225) for 2 weeks beginning at birth in CNPase-hEGFR mice normalized all pathologies at 3 months of age as evaluated by hotplate testing or histology and by electron microscopy. Mast cell chemoattractants brain-derived neurotrophic factor, monocyte chemoattractant protein-1, and transforming growth factor-beta1, which may account for mast cell accumulation and fibrosis, were reduced by cetuximab. Later treatment was much less effective. A birth to 2-week pulse of cetuximab blocked hEGFR phosphorylation and Schwann cell prolifera-tion in perinatal mutant nerve, so CNPase-hEGFR Schwann cell numbers correlate with the cetuximab effect. A >250-fold enlarged population of EGFR(+)/p75(+) cells was detected in newborn Nf1(+/-) mouse nerves. These results suggest the existence of an EGFR(+) cell enriched in the perinatal period capable of driving complex changes characteristic of neurofibroma formation. |
