Characterization of newly established tumor lines from a spontaneous malignant schwannoma in F344 rats: nerve growth factor production, growth inhibition by transforming growth factor-beta1, and macrophage-like phenotype expression

Acta Neuropathol. 2003 Sep;106(3):221-33. doi: 10.1007/s00401-003-0723-0. Epub 2003 Jun 17.


Transplantable tumor (KE) and clone cell (KE-F11) lines were established from a spontaneous malignant schwannoma found in an aged F344 rat. The primary tumor and KE tumors consisted of oval or spindle cells arranged in ill-defined bundles. Cultured KE-F11 cells exhibited polygonal or spindle configurations. Immunohistochemically, neoplastic cells in KE and KE-F11 reacted to vimentin, S-100 protein, neuron-specific enolase, myelin basic protein, and glial fibrillary acidic protein in varying degrees, indicating neurogenic features; occasional cells reacted to alpha-smooth muscle actin. Cells positive for lysosomal enzymes (acid phosphatase and non-specific esterase), and ED1 (rat macrophage specific) were observed in KE-F11, and electron microscopically, cells with many lysosomes were frequently present, indicating expression of macrophage-like phenotypes. Bioassay analysis revealed that KE-F11 cells produced high levels of nerve growth factor. DNA synthesis was inhibited by addition of transforming growth factor-beta1 (TGF-beta1), and Northern blot analysis revealed that expression of c-myc, a cell cycle-related immediate early gene, was depressed by TGF-beta1. Likely, TGF-beta1 is a factor capable of inhibiting cellular growth of Schwann cells. mRNA expression of the low-density lipoprotein receptor-related protein (LRP) was seen in KE-F11 cells by Northern blot analysis, and the level was decreased by lipopolysaccharide (LPS) treatment. LRP may be attributable to regulation of Schwann cell functions. KE-F11 cells seeded on laminin-coated dishes exhibited more extended cytoplasmic projections than on collagen type I-coated dishes. The present study provides evidence that biological properties of malignant schwannoma-derived cells might be affected by exogenous factors such as TGF-beta1, LPS and laminin. These tumor lines may be useful for studies on pathobiological characteristics of Schwann cells.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / metabolism
  • Animals
  • Blotting, Northern
  • Cell Count
  • Cell Line, Transformed
  • Desmin / metabolism
  • Dose-Response Relationship, Drug
  • Genes, jun / physiology
  • Genes, myc / physiology
  • Glial Fibrillary Acidic Protein / metabolism
  • In Vitro Techniques
  • Keratins / metabolism
  • Lipopolysaccharides / pharmacology
  • Macrophages / pathology
  • Macrophages / ultrastructure*
  • Male
  • Microscopy, Electron
  • Myelin Basic Protein / metabolism
  • Nerve Growth Factor / metabolism*
  • Neurilemmoma / metabolism*
  • Neurilemmoma / pathology
  • Neurilemmoma / ultrastructure
  • PC12 Cells
  • Phenotype
  • Phosphopyruvate Hydratase / metabolism
  • RNA, Messenger / biosynthesis
  • Rats
  • Rats, Inbred F344
  • Reverse Transcriptase Polymerase Chain Reaction / methods
  • S100 Proteins / metabolism
  • Staining and Labeling
  • Time Factors
  • Transforming Growth Factor beta / metabolism*
  • Transforming Growth Factor beta1
  • Vimentin / metabolism


  • Actins
  • Desmin
  • Glial Fibrillary Acidic Protein
  • Lipopolysaccharides
  • Myelin Basic Protein
  • RNA, Messenger
  • S100 Proteins
  • Tgfb1 protein, rat
  • Transforming Growth Factor beta
  • Transforming Growth Factor beta1
  • Vimentin
  • Keratins
  • Nerve Growth Factor
  • Phosphopyruvate Hydratase