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Characterization of newly established tumor lines from a spontaneous malignant schwannoma in F344 rats: nerve growth factor production, growth inhibition by transforming growth factor-β1, and macrophage-like phenotype expression

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Abstract

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 α-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-β1 (TGF-β1), and Northern blot analysis revealed that expression of c-myc, a cell cycle-related immediate early gene, was depressed by TGF-β1. Likely, TGF-β1 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-β1, LPS and laminin. These tumor lines may be useful for studies on pathobiological characteristics of Schwann cells.

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Acknowledgement

This study was supported in part by Grant-in-Aid (No. 12660287) for Scientific Research C, the Ministry of Education, Science, Sports and Culture, Japan.

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Authors and Affiliations

  1. Laboratories of Veterinary Pathology and Anatomy, Graduate School of Agriculture and Biological Sciences, Osaka Prefecture University, Gakuencho 1-1, Sakai, 599-8531, Osaka, Japan

    J. Yamate, H. Yasui, Y. Tsukamoto, M. Kuwamura, D. Kumagai & S. Sakuma

  2. Department of Biomedical Sciences, University of Guelph, Guelph, Ontario, N1G 2W1, Canada

    S. J. Benn & J. LaMarre

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  1. J. Yamate
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  2. H. Yasui
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Correspondence to J. Yamate.

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Yamate, J., Yasui, H., Benn, S.J. et al. Characterization of newly established tumor lines from a spontaneous malignant schwannoma in F344 rats: nerve growth factor production, growth inhibition by transforming growth factor-β1, and macrophage-like phenotype expression. Acta Neuropathol 106, 221–233 (2003). https://doi.org/10.1007/s00401-003-0723-0

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