NF1 Tumor Specific Therapeutic Modeling

Abstract

Abstract : The goal of this project is to establish an animal model of plexiform neurofibroma which then can be used to test emerging anticancer therapies for the management of tumor growth in NFl patients. The first specific aim is to establish a syngraft model of NFl tumorigenesis. Progress toward this aim includes: a) established and characterized numerous Schwann cell cultures from wild-type and heterozygous and homozygous and homozygous null NFl knockout mouse embryos; b)documented several lines of evidence that Nfl-/- Schwann cell have a growth advantage in vitro; c)effectively transfected Nf1-/- Schwann cell cultures with AAV-GFP; d)implanted GFP-labeled Nf1-/- cells in mouse nerve and detected them with GFP immunohisto-chemistry; e) documented tumorigenic growth by Nf1-/- Schwann cells implanted in the nerves of adult mice and; f) established a highly relevant syngraft model by implanting Nf1-/- Schwann cell into mice with and Nfl background. The second aim is to establish a xenograft model to examine the growth of human neurofibroma tumor cells. Progress toward this aim includes: a)established a breeding colony of Nf1-/- scid mice to be used as hosts for tumor grafts; b)achieved sizeable tumors by engrafting human NFl Schwann cells in mouse nerves; c)provide a thorough characterization of human NFl schwann cells cultures and their tumorigenic properties; d) achieve NMR methods to access tumor growth within the mouse nerve and; e)assess tumorigenic growth and neovascularization by engrafted NFl tumor cells.