1. ¹Department of Neuroscience, College of Medicine, University of Florida, Gainesville, FL, USA
2. ²Shands Cancer Center, College of Medicine, University of Florida, Gainesville, FL, USA
3. ³Department of Molecular Genetics and Microbiology, College of Medicine, University of Florida, Gainesville, FL, USA
4. ⁴Department of Biomedical Engineering, College of Medicine, University of Florida, Gainesville, FL, USA
5. ⁵Department of Orthopaedics and Rehabilitation, College of Medicine, University of Florida, Gainesville, FL, USA
6. ⁶Department of Pathology and Laboratory Medicine, College of Medicine, University of Florida, Gainesville, FL, USA
7. ⁷Department of Pediatrics, Genetics Division, College of Medicine, University of Florida, Gainesville, FL, USA
8. ⁸Department of Biochemistry and Molecular Biology, College of Medicine, University of Florida, Gainesville, FL, USA
9. ⁹Department of Pediatrics, Neurology Division, College of Medicine, University of Florida, Gainesville, FL, USA

Correspondence: Dr GQ Perrin, PhD, Department of Neuroscience, College of Medicine, University of Florida, PO Box 100244, 1600 SW Archer Rd, Gainesville, FL 32610-0244, USA. E-mail: gperrin@ufl.edu

Received 4 May 2007; Revised 15 August 2007; Accepted 16 August 2007; Published online 17 September 2007.

Abstract

Malignant peripheral nerve sheath tumors (MPNST) are the most aggressive cancers associated with neurofibromatosis type 1 (NF1). Here we report a practical and reproducible model of intraneural NF1 MPNST, by orthotopic xenograft of an immortal human NF1 tumor-derived Schwann cell line into the sciatic nerves of female scid mice. Intraneural injection of the cell line sNF96.2 consistently produced MPNST-like tumors that were highly cellular and showed extensive intraneural growth. These xenografts had a high proliferative index, were angiogenic, had significant mast cell infiltration and rapidly dominated the host nerve. The histopathology of engrafted intraneural tumors was consistent with that of human NF1 MPNST. Xenograft tumors were readily examined by magnetic resonance imaging, which also was used to assess tumor vascularity. In addition, the intraneural proliferation of sNF96.2 cell tumors was decreased in ovariectomized mice, while replacement of estrogen or progesterone restored tumor cell proliferation. This suggests a potential role for steroid hormones in supporting tumor cell growth of this MPNST cell line in vivo. The controlled orthotopic implantation of sNF96.2 cells provides for the precise initiation of intraneural MPNST-like tumors in a model system suitable for therapeutic interventions, including inhibitors of angiogenesis and further study of steroid hormone effects on tumor cell growth.