Plexiform-like neurofibromas develop in the mouse by intraneural xenograft of an NF1 tumor-derived Schwann cell line.

Abstract

Plexiform neurofibromas are peripheral nerve sheath tumors that arise frequently in neurofibromatosis type 1 (NF1) and have a risk of malignant progression. Past efforts to establish xenograft models for neurofibroma involved the implantation of tumor fragments or heterogeneous primary cultures, which rarely achieved significant tumor growth. We report a practical and reproducible animal model of plexiform-like neurofibroma by xenograft of an immortal human NF1 tumor-derived Schwann cell line into the peripheral nerve of scid mice. The S100 and p75 positive sNF94.3 cell line was shown to possess a normal karyotype and have apparent full-length neurofibromin by Western blot. These cells were shown to have a constitutional NF1 microdeletion and elevated Ras-GTP activity, however, suggesting loss of normal neurofibromin function. Localized intraneural injection of the cell line sNF94.3 produced consistent and slow growing tumors that infiltrated and disrupted the host nerve. The xenograft tumors resembled plexiform neurofibromas with a low rate of proliferation, abundant extracellular matrix (hypocellularity), basal laminae, high vascularity, and mast cell infiltration. The histologic features of the developed tumors were particularly consistent with those of human plexiform neurofibroma as well. Intraneural xenograft of sNF94.3 cells enables the precise initiation of intraneural, plexiform-like tumors and provides a highly reproducible model for the study of plexiform neurofibroma tumorigenesis. This model facilitates testing of potential therapeutic interventions, including angiogenesis inhibitors, in a relevant cellular environment.

• Authors: George Q Perrin, Lauren Fishbein, Susanne A Thomson, Stacey L Thomas, Karen Stephens, James Y Garbern, George H DeVries, Anthony T Yachnis, Margaret R Wallace, David Muir
• Journal: Journal of neuroscience research (J Neurosci Res) Vol. 85 Issue 6 Pg. 1347-57 (May 01 2007) ISSN: 0360-4012 [Print] United States
• PMID: 17335073 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S.)
• Copyright: (c) 2007 Wiley-Liss, Inc.

Chemical References

• Nerve Tissue Proteins
• Neurofibromin 1
• ras Proteins

Topics

• Adult
• Animals
• Blotting, Western
• Cell Line, Tumor
• Female
• Humans
• Lung Neoplasms (pathology)
• Mice
• Mice, SCID
• Neoplasm Transplantation (methods)
• Nerve Tissue Proteins (metabolism)
• Neurofibromatosis 1 (pathology)
• Neurofibromin 1 (genetics)
• Schwann Cells (cytology, enzymology)
• Transplantation, Heterologous (methods)
• ras Proteins (metabolism)