Summary
S-100 protein, a soluble protein restricted to the nervous system, was measured by complement fixation in 51 neurogenic and non-neurogenic tumors produced by either methylnitrosourea or ethylnitrosourea in three different strains of rats.
Nineteen of the 51 neurogenic tumors were neoplasms of the central nervous system (18 of the brain, 1 of the spinal cord). They were diagnosed morphologically as 5 mixed gliomas, 4 anaplastic gliomas, 4 glioependymomas, 1 ependymoma, 3 gliosarcomas, and 2 unclassified tumors. With the exception of one anaplastic glioma and one gliosarcoma, all other central nervous system tumors contained S-100 protein, ranging from 0.005–0.13% of the total 35000 g supernatant protein.
S-100 protein was also demonstrated in 21 of the 22 tumors of the peripheral nervous system, originating from the trigeminal nerves, the spinal roots, and from peripheral nerves. The average S-100 protein content of these tumors was 0.2% (range 0.02–1.6%). A possible correlation between S-100 protein content and tumor differentiation must be evaluated.
S-100 protein was detected in only one of 10 neoplasms morphologically classified as non-neurogenic (7 sarcomas, 2 carcinomas, and 1 hemangioendothelioma). On the basis of its S-100 protein content, one tumor was reclassified as a neurosarcoma.
The sensitivity and the high degree of specificity of the S-100 protein assay makes it a useful biochemical tool for the identification of neurogenic tumors. The presence of S-100 protein must be considered as a definitive indication for neural cell participation in neoplastic growth.
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References
Amano, T., Richelson, E., Nirenberg, M.: Neurotransmitter synthesis by neuroblastoma clones. Proc. nat. Acad. Sci. (Wash.)69, 258–263 (1972).
Augusti-Tocco, G., Sato, G.: Establishment of functional clonal lines of neurons from mouse neuroblastoma. Proc. nat. Acad. Sci. (Wash.)64, 311–315 (1969).
Benda, P.: Protéine S-100 et tumeurs cérébrales humaines. Rev. neurol.118, 368–372 (1968).
Benda, P., Someda, K., Messer, J., Sweet, W. H.: Morphological and immunochemical studies of rat glial tumors and clonal strains propagated in culture. J. Neurosurg.34, 310–323 (1971).
Calissano, P., Moore, B. W., Friesen, A.: Effect of calcium on S-100, a protein of the nervous system. Biochemistry8, 4318–4326 (1969).
Cicero, T. J., Cowan, W. M., Moore, B. W., Suntzeff, V.: The cellular localization of the two brain specific proteins, S-100 and 14-3-2. Brain Res.18, 25–34 (1970).
Haglid, K. G., Carlsson, C. A.: An immunological study of some human brain tumors concerning the brain specific protein S-100. Neurochirurgia (Stuttg.)14, 24–27 (1971).
Haglid, K. G., Carlsson, C. A., Thulin, C. A.: Lactate dehydrogenase isoenzymes and proteins in human gliomas. Neurochirurgia (Stuttg.)13, 19–28 (1970).
Koestner, A., Swenberg, J. A., Wechslei, W.: Transplacental production with ethylnitrosourea of neoplasms of the nervous system in Sprague-Dawley rats. Amer. J. Path.63, 37–50 (1971).
Koestner, A., Swenberg, J. A., Wechsler, W.: Experimental tumors of the nervous system induced by resorptive N-nitrosourea-compounds. Progr. exp. Tumor Res. (Basel)17, 9–30 (1972).
Levine, L.: Microcomplement fixation. In: D. M. Weir (ed.): Handbook of Experimental Immunochemistry, pp. 709–719. Oxford: Blackwell Scientific Publications 1967.
Levine, L., Moore, B. W.: Structural relatedness of a vertebrate brain acidic protein as measured immunochemically. Neurosci. Res. Progr. Bull.3, 18–22 (1965).
Lowry, O. H., Rosebrough, W. F., Farr, A. L., Randall, R. V.: Protein measurement with the folin phenol reagent. J. biol. Chem.193, 265–275 (1951).
McEwen, B. S., Hyden, H.: A study of specific brain proteins on the semi-micro scale. J. Neurochem.13, 823–833 (1965).
Moore, B. W.: A soluble protein characteristic of the nervous system. Biochem. biophys. Res. Commun.19, 739–744 (1965).
Moore, B. W., McGregor, D. J.: Chromatographic and electrophoretic fractionation of soluble proteins of brain and liver. J. biol. Chem.240, 1647–1653 (1965).
Moore, B. W., Perez, V. S.: In: Physiological and biochemical aspects of nervous integration, pp. 343–359. F. D. Carlson, ed. Englewood Cliffs, N. J.: Prentice Hall, Inc. 1968.
Moore, B. W., Perez, V. J., Gehring, M.: Assay and regional distribution of a soluble protein characteristic of the nervous system. J. Neurochem.15, 265–272 (1968).
Perez, V. J., Olney, J. W., Cicero, T. J., Moore, B. W., Bahu, B. A.: Wallerian Degeneration in rabbit optic nerve: cellular localization in the central nervous system of the S-100 and 14-3-2 proteins. J. Neurochem.17, 511–519 (1970).
Pfeiffer, S. E., Wechsler, W.: Isolation of clones from a chemically induced tumor of the peripheral nervous system of the rat. Naturwissenschaften59, 518–519 (1972a).
Pfeiffer, S. E., Wechsler, W.: Biochemically differentiated neoplastic clone of Schwann cells. Proc. Nat. Acad. Sci.69, 2885–2889 (1972b).
Pfeiffer, S. E., Kornblith, P. L., Cares, H. L., Seals, J., Levine, L.: S-100 protein in human acoustic neurinomas. Brain Res.41, 187–193 (1972).
Slagel, D. E., Wilson, C. B., Simmons, P. B.: Polyacrylamide electrophoresis and immunodiffusion studies of brain tumor proteins. Ann. N. Y. Acad. Sci.159, 490–496 (1969).
Stavrou, D., Haglid, K. G., Weidenbach, W.: The brain specific proteins S-100 and 14.3.2 in experimental brain tumors of the rat. Z. ges. exp. Med.156, 237–242 (1971).
Swenberg, J. A., Koestner, A., Wechsler, W.: The induction of tumors of the nervous system with intravenous methylnitrosourea. Lab. Invest.26, 74–85 (1972).
Uyemura, K., Vincendon, G., Gombos, G., Mandel, P.: Purification and some properties of S-100 protein fractions from sheep and pig brains. J. Neurochem.18, 429–439 (1971).
Wechsler, W., Kleihues, P., Matsumoto, S., Zülch, K. J., Ivankovic, S., Preussmann, R., Druckrey, H.: Pathology of experimental neurogenic tumors chemically induced during prenatal and postnatal life. Ann. N. Y. Acad. Sci.159, 360–408 (1969).
Wechsler, W., Pfeiffer, S. E., Swenberg, J. A., Koestner, A.: S-100 Protein in experimental rat tumors of the central and peripheral nervous system. Naturwissenschaften59, 370–371 (1972).
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Wechsler, W., Pfeiffer, S.E., Swenberg, J.A. et al. S-100 protein in methyl- and ethylnitrosourea induced tumors of the rat nervous system. Acta Neuropathol 24, 287–303 (1973). https://doi.org/10.1007/BF00685585
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DOI: https://doi.org/10.1007/BF00685585