Summary
A pigmented tumor fraction, designated IB-9, obtained following cellular dissociation and elutriation procedures applied to the solid transplants of the OTT-6050 mouse teratoma cell line, was characterized enzymatically and by immunofluorescence for the presence of tyrosinase and tyrosine hydroxylase (TH). Enzymatic assays of the pigmented tumors were compared with those obtained on non-pigmented teratoma-derived tumors, on pigmented tumors obtained from the mouse melanoma B16 line as a control for tyrosinase activity, and on whole brains of adult 129/J mice as a control for TH activity.
All the teratoma-derived tumors, including the IB-9 fraction, showed a predominance of TH over tyrosinase activity. The levels of TH activity appeared independent of the presence or the extent of melanin pigment. All pigmented teratoma-derived tumors showed low levels of tyrosinase activity.
On the basis of the enzymatic assays, the IB-9 tumors were divided into two groups: group I, which showed low enzyme activity, almost certainly entirely tyrosinase; and group II, in which the enzyme activity appeared largely due to TH, with presumably a very low background of tyrosinase activity. Immunofluorescence demonstrated the localization of TH activity to non-pigmented cells of the IB-9 fraction, whereas the pigmented cells showed absence of TH activity.
These findings, taken in conjunction with the presence by electron microscopy of premelanosomes and melanosomes, indicate that pigment formation associated with melanosomal differentiation in the neural cells of IB-9 with the histologic patterns of primitive CNS neuroepithelium results from tyrosinase activity only and is therefore unrelated to the metabolic pathways involved in catecholamine synthesis and degradation. It is suggested that, at this stage of differentiation and in this system, the expression of catecholamine synthesis via tyrosine hydroxylase in neuroepithelial cells, and of melanin pigment via tyrosinase, are probably mutually exclusive.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Bagnara JT, Matsumoto J, Ferris W, Frost SK, Turner WA, Tchen TT, Taylor JD (1979) Common origin of pigment cells. Science 203:410–415
Barden H (1969) The histochemical relationship of neuromelanin and lipofuscin. J Neuropathol Exp Neurol 28:419–441
Barden H (1975) The histochemical relationships and the nature of neuromelanin. Aging 1:79–112
Boesel CP, Suhan JP, Sayers MP (1978) Melanotic medulloblastoma: report of a case with ultrastructural findings. J Neuropathol Exp Neurol 37:531–543
Boesel CP, Suhan JP (1979) A pigmented choroid plexus carcinoma: histochemical and ultrastructural studies. J Neuropathol Exp Neurol 38:177–186
Dehner LP, Sauk JJ Jr, Vickers RA (1976) Aggressive pigmented neuroectodermal tumor of infancy: histologic, ultrastructural and in vitro characterization. Lab Invest 34:313 (abstr.)
Dehner LP, Sibley RK, Sauk JJ, Vickers RA, Nesbit ME, Leonard AS, Waite DE, Neeley JE, Ophoven J (1979) Malignant melanotic neuroectodermal tumor of infancy: a clinical, pathological, ultrastructural, and tissue culture study. Cancer 43:1389–1410
Edelman AM, Raese JD, Lazar MA, Barchas JD (1981) Tyrosine hydroxylase from brain: phosphorylation of the enzyme by cyclic AMP-dependent protein kinase. J Pharmacol Exp Ther (In press)
Edelstein LM (1971) Melanin, a unique biopolymer. Pathobiol Ann 1:309–324
Graham DG (1978) Oxidative pathways for catecholamines in the genesis of neuromelanin and cytotoxic quinones. Mol Pharmacol 14:633–643
Graham DG (1979) On the origin and significance of neuromelanin. Arch Pathol Lab Med 103:359–362
Hahn JF, Sperber EE, Netsky MG (1976a) Melanotic neuroectodermal tumors of the brain and skull. J Neuropathol Exp Neurol 35:508–519
Hahn JF, Netsky MG, Butler AB, Sperber EE (1976b) Pigmented ganglioneuroblastoma: relation of melanin and lipofuscin to schwannomas and other tumors of neural crest origin. J Neuropathol Exp Neurol 35:393–403
Hayward AF, Fickling BW, Lucas RB (1969) An electron microscope study of a pigmented tumour of the jaw of infants. Br J Cancer 23:702–708
Herrick MK, Rubinstein LJ (1979) The cytological differentiating potential of pineal parenchymal neoplasms (true pinealomas). A clinicopathological study of 28 tumours. Brain 102:289–320
Ichiyama A, Nakamura S, Nishizuka Y, Hayaishi O (1970) Enzymic studies on the biosynthesis of serotonin in mammalian brain. J Biol Chem 245:1699–1709
Ishikawa G, Takagi M, Ito H (1967) Histopathology of melanotic tumor of the jaw of the infant. J Dental Res 46:1259 (abstr.)
Lana-Peixoto MA, Lagos J, Silbert SW (1977) Primary pigmented carcinoma of the choroid plexus. A light and electron microscopic study. J Neurosurg 47:442–450
McCloskey JJ, Parker JC Jr, Brooks WH, Blacker HM (1976) Melanin as a component of cerebral gliomas. The melanotic cerebral ependymoma. Cancer 37:2373–2379
Mann DMA, Yates PO (1974) Lipoprotein pigments-their relationship to ageing in the human nervous system. II. The melanin content of pigmented nerve cells. Brain 97:489–498
Marsden CD (1969) Pigments in pathology. Academic Press, Inc. London, p. 395
Mennemeyer RP, Hammar SP, Tytus JS, Hallman KO, Raisis JE, Bockus D (1979) Melanotic schwannoma: clinical and ultrastructural studies of three cases with evidence of intracellular melanin synthesis. Am J Surg Pathol 3:3–10
Misugi K, Okajima H, Newton WA, Kmetz DR, DeLorimier AA (1965) Mediastinal origin of a melanotic progonoma or retinal anlage tumor. Ultrastructural evidence for neural crest origin. Cancer 18:477–484
Mullins JD (1980) A pigmented differentiating neuroblastoma: a light and ultrastructural study. Cancer 46:522–528
Nagatsu T, Levitt M, Udenfriend S (1964) Tyrosine hydroxylase. The initial step in norepinephrine biosynthesis. J Biol Chem 239:2910–2917
Neustein HB (1967) Fine structure of a melanotic progonoma or retinal anlage tumor of the anterior fontanel. Exp Molec Pathol 6:131–142
Nožička Z, Špaček J (1978) Melanotic neuroectodermal tumor of infancy with highly differentiated neural component: light and electron microscopic study. Acta Neuropathol 44:229–233
Orenberg EK, VandenBerg SR, Barchas JD, Herman MM (1976) Neurochemical studies in a mouse teratoma with neuroepithelial differentiation: presence of cyclic AMP, serotonin and enzymes of the serotonergic, adrenergic and cholinergic systems. Brain Res 101:273–281
Palacios JJN (1980) Malignant melanotic neuroectodermal tumor. Light and electron microscopic study. Cancer 46:529–536
Pomerantz SH (1963) Separation, purification, and properties of two tyrosinases from hamster melanoma. J Biol Chem 238:2351–2357
Raese JD, Makk G, Barchas JD (1981) Multiple forms of tyrosine hydroxylase; isolation, characterization and phosphorylation by a cyclic nucleotide independent protein kinase. Proceedings of Second Conference on Monoamine Enzymes, Airlie House, Warrenton, Virginia (In press)
Russell DS, Rubinstein LJ (1977) Pathology of tumours of the nervous system, 4th ed. Edward Arnold, London, pp 211–212
Seiji M, Fitzpatrick TB (1961) The reciprocal relationship between melanization and tyrosinase activity in melanosomes (melanin granules). J Biochem 49:700–706
Seiji M, Sasaki M, Tomita Y (1978) Nature of tyrosinase inactivation in melanosomes. Tohoku J Exp Med 125:233–245
Spence AM, Rubinstein LJ, Conley FK, Herman MM (1976) Studies on experimental malignant nerve sheath tumors maintained in tissue and organ culture systems. III. Melanin pigment and melanogenesis in experimental neurogenic tumors. A reappraisal of the histogenesis of pigmented nerve sheath tumors. Acta Neuropathol 35:27–45
Sung JH, Mastri AR, Segal EL (1973) Melanotic medulloblastoma of the cerebellum. J Neuropathol Exp Neurol 32:437–445
Swan GA (1974) Structure, chemistry and biosynthesis of the melanins. Fortschr Chem Org Naturst 31:521–582
Taira Y, Nakayama I, Moriuchi A (1978) Histologic and fine structural studies on pigmented neuroectodermal tumor of infancy. Acta Path Jap 28:83–98
Ule G, Berlet H, Riedl H, Fankhauser R, Volk B (1979) Über Melanin und Melanosomen im ZNS im Vergleich zu extracerebralen Erscheinungsformen und synthetischem Melanin aus Dopamin und Serotonin. Acta Neuropathol 48:177–188
VandenBerg SR, Herman MM, Ludwin SK, Bignami A (1975) An experimental mouse testicular teratoma as a model for neuroepithelial neoplasia and differentiation. I. Light microscopic and tissue and organ culture observations. Am J Pathol 79:147–168
VandenBerg SR, Hess JR, Herman MM, DeArmond SJ, Halks-Miller M, Rubinstein LJ (1981) Neural differentiation in the OTT-6050 mouse teratoma. Production of a tumor fraction showing melanogenesis in neuroepithelial cells after centrifugal elutriation. Virchows Arch Abt A [Pathol Anat] (in press)
Waymire JC, Bjur R, Weiner N (1971) Assay of tyrosine hydroxylase by coupled decarboxylation of DOPA formed from 1-14C-L-tyrosine. Anal Biochem 43:588–600
White R, Hu F (1977) Characteristics of tyrosinase in B16 melanoma. J Invest Derm 68:272–276
White R, Hanson GC, Hu F (1979) Tyrosinase maturation and pigment expression in B16 melanoma: relation to theophylline treatment and intracellular cAMP. J Cell Physiol 99:441–450
Zajtchuk JT, Lunsford TM, Alford TJ (1978) Melanotic neuroectodermal tumor of infancy. A case report. Laryngoscope 88:342–347
Author information
Authors and Affiliations
Additional information
Supported by Research Grant CA 11689 of the National Cancer Institute; MH 23861 of the National Institute of Mental Health; and Neuropathology Training Grant NS 5 T32 NS 7111 of the National Institute of Neurological and Communicative Diseases and Stroke, USPHS
Rights and permissions
About this article
Cite this article
Erdelyi, E., VandenBerg, S.R., Raese, J. et al. Neural differentiation in the OTT-6050 mouse teratoma: Enzymatic and immunofluorescence characterization of a tumor fraction showing melanogenesis in neuroepithelial cells. Virchows Arch. A Path. Anat. and Histol. 393, 27–37 (1981). https://doi.org/10.1007/BF00430868
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00430868