Summary
Skin fibroblasts and tumor cells were cultured from four patients with peripheral von Recklinghausen's neurofibromatosis (NF). The cell type enriched in culture from the tumors carried the fibroblastic Thy 1.1. cell surface antigen and produced fibronectin, like fibroblasts from skin of NF-patients or from control persons. In electron micrographs the NF tumor and NF skin cells were similar to the control skin fibroblasts; elongated in shape, contained tubular mitochondria, variable amounts of granular endoplasmic reticulum, numerous lysosomal inclusion bodies and collections of 5 nm filaments. Trypsinized cells were fractionated with centrifugation in a Percoll density gradient. All cell lines produced only one sharp band of viable cells at the buoyant density of 1.03.
Compared with the NF skin or control skin fibroblasts the NF tumor cells, however, produced a less well organized peri-and extracellular matrix estimated from fibronectin fluorescence. The nuclear sizes were measured from photographs of the cultures. The nuclei of all four tumor cell lines were larger than those of the skin fibroblasts of the corresponding patients. Neurofibromatosis tumor cells thus resemble skin fibroblasts in their density and in some ultrastructural properties but are different in their growth pattern and synthetic functions.
Similar content being viewed by others
References
Adams RD (1979) Neurocutaneous diseases. In: Fitzpatric TB, Eisen AZ, Wolff K, Friedberg IM, Austen KF (eds) Dermatology in general medicine, 2nd edn. McGraw Hill, New York, pp. 1206–1245
Askanas V, Engel WK, Dalakas MC, Lawrence JC, Carter LS (1980) Human Schwann cells in tissue culture. Histochemical and ultrastructural studies. Arch Neurol 37:329–337
Arstila AU, Hirsimäki P, Trump BF (1974) Studies on the subcellular pathophysiology of sublethal chronic cell injury. Beitr Pathol Anat 152:211–242
Fields KL, Brockes JP, Mirsky R, Wendon LMB (1978) Cell surface markers for distinguishing different types of rat dorsal root ganglion cells in culture. Cell 14:43–51
Greene JF, Fitzwater JE, Burgess J (1974) Arterial lesions associated with neurofibromatosis. Am J Clin Pathol 82:481–487
Hedman K, Vaheri A, Wartiovaara J (1978) External fibronectin of cultured human fibroblasts is predominantly a matrix protein. J Cell Biol 76:748–760
Kamensky E, Philippart M, Cancilla P, Frommes SP (1973) Cultured skin fibroblasts in storage disorders. Am J Pathol 73:59–80
Kurkinen M, Alitalo K (1979) Fibronectin and procollagen produced by a clonal line of Schwann cells. FEBS Lett 102:64–68
Lott IT, Richardson EP (1981) Neuropathological findings and the biology of neurofibromatosis. adv Neurol 29:23–32
Lucky AW, Mahoney MJ, Barrnett RJ, Rosenberg LE (1975) Electron microscopy of human skin fibroblasts in situ during growth in culture. Exp Cell Res 92:383–393
Olden K, Yamada KM (1977) Mechanism of the decrease in the major cell surface protein in chick embryo fibroblasts after transformation. Cell 11:957–969
Pharmacia Fine Chemicals (1980) Percoll methodology and applications. Density marker beads for calibration of gradients of Percoll.
Peltonen J, Marttala T, Vihersaari T, Renvall S, Penttinen R (1981) Collagen synthesis in cells cultured from v. Recklinghausen's neurofibromatosis. Acta Neuropathol (Berl) 55:183–187
Penttinen R, Frey H, Aalto M, Vuorio E, Marttala T (1980) Collagen synthesis in cultured cells. In: Viidik A, Vuust J (eds) Biology of collagen. Academic Press, London New York, pp 87–103
Raff MC, Fields KL, Hakomori S-I, Mirsky R, Pruss RM, Winter J (1979) Cell-type-specific markers for distinguishing and studying neurons and the major classes of glial cells in culture. Brain Res 174:283–308
Riccardi VM, Maragos VA (1980) Pathophysiology of neurofibromatosis. I. Resistance in vitro to nitrotyrosine as an experission of the mutation. In Vitro 16:706–714
Riccardi VM, Maragos VA (1981) Characteristics of skin and tumor fibroblasts from neurofibromatosis patients. Adv Neurol 29:191–198
Stenman S, Wartiovaara J, Vaheri A (1977) Changes in the distribution of a major fibroblasts protein, fibronectin, during mitosis and interphase. J Cell Biol 74:453–458
Vaheri A, Ruoslahti E, Westermark B, Pontén J (1976) A common cell-type specific surface antigen in cultured human glial cells and fibroblasts: loss in malignant cells. J Exp Med 143:64–72
Winter RB, Moe JH, Bradford DS, Lonstein JE, Pedras CV, Weber AH (1979) Spine deformity in neurofibromatosis. A review of one hundred and two patients. J Bone Joint Surg 61A:677–694
Zelkovitz M, Stambouly J (1980) Diminished epidermal growth factor binding by neurofibromatosis fibroblasts. Ann Neurol 8(3):296–299
Zelkowitz M (1981) Neurofibromatosis fibroblasts: abnormal growth and binding to epidermal growth factor. Adv Neurol 29:67–75
Yamada KM, Yamada SS, Pastan I (1977) Quantitation of a transformation-sensitive adhesive cell surface glycoprotein. J Cell Biol 74:649–654
Author information
Authors and Affiliations
Additional information
Financially supported by grants (to J.P.) from the Research and Scientific Foundation of Lääke Oy Ltd. and from the Emil and Blida Maunula Foundation, and by institutional grants from the Turku University Foundation and the Sigrid Jusélius Foundation
Rights and permissions
About this article
Cite this article
Peltonen, J., Aho, H., Rinne, U.K. et al. Neurofibromatosis tumor and skin cells in culture. Acta Neuropathol 61, 275–282 (1983). https://doi.org/10.1007/BF00691998
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00691998