Summary
The aim of the present study was to evaluate the putative photoreceptor differentiation found in certain cerebellar medulloblastomas. The analyses were focussed on S-antigen, rod-opsin (the apoprotein of the visual pigment rhodopsin) and 11-cis retinal (the prosthetic group of rhodopsin). Fresh frozen and paraffinembedded biopsy specimens of three medulloblastomas were investigated by means of immunocytochemistry, enzyme-linked immunosorbent assay (ELISA), high-pressure liquid chromatography (HPLC), and immunoblotting. As shown in paraffin sections, one out of the three tumors (tumor A) contained S-antigen- and rod-opsin-immunoreactive tumor cells. The immunoblotting technique revealed in this tumor a single protein band of approximately 48–50 kDa that reacted with the S-antigen antibody and three protein bands of approximately 40, 75 and 110 kDa recognized by the rod-opsin antibody. These bands could not be detected in the two remaining tumors (tumor B and C). The rod-opsin content of tumor A was quantified by the ELISA; 11.7 pmol rod-opsin were calculated for the biopsy. The HPLC demonstrated the presence of 11-cis- and all-trans-retinal in tumor A, but not in tumors B and C. Furthermore, it was shown that 11-cis-retinal was converted to all-trans-retinal upon illumination of the tumor extract. The ratio between 11-cis-and all-trans-retinal was approximately 1:1 before illumination and 3:5 after illumination. A total of 2–3 pmol of retinal was found in the biopsy of tumor A. In addition all-trans-retinol was present in this tumor. The results indicate that certain medulloblastomas express a functional photopigment and S-antigen, another protein of the phototransduction cascade. They strongly support the concept that medulloblastoma cells may differentiate along the photoreceptor cell lineage.
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References
Bailey B, Cushing H (1925) Medulloblastoma cerebelli: a common type of midcerebellar glioma of childhood. Arch Neuropathol Psychiatry 14:192–224
Bok D, Heller J (1976) Transport of retinol from the blood to the retina: an autoradiographic study of the pigment epithelial cell surface receptor for plasma retinol binding protein. Exp Eye Res 22:395–402
Bonnin JM, Perentes E (1988) Retinal S-antigen immunoreactivity in medulloblastomas. Acta Neuropathol 76:204–207
Bridges CDB (1976) Vitamin A and the role of the pigment epithelium during bleaching and regeneration of rhodopsin in the frog eye. Exp Eye Res 22:435–455
Bridges CDB (1977) Rhodopsin regeneration in rod outer segments: utilization of 11-cis retinal and retinol. Exp Eye Res 24:571–580
Bridges CDB, Fong SL, Liou GI, Alvarez RA, Landers RA (1983) Transport, utilization and metabolism of visual cycle retinoids in the retina and pigment epithelium. In: Osborne NN, Chader GJ (eds) Progress in retinal research, vol 2. Pergamon Press, Oxford New York, pp 137–162
Bridges CDB, Landers RA, Fong SL, Liou GI (1986) Interstitial retinol-binding protein (IRBP) in rat and bovine pineal organs: evolutionary vestige or functional molecule? In: O'Brien P, Klein DC (eds) Pineal and retinal relationships. Academic Press, New York, pp 383–400
Burger PC, Grahmann FC, Bliestle A, Kleihues P (1987) Differentiation in the medulloblastoma. A histological and immunohistochemical study. Acta Neuropathol (Berl) 73:115–123
Burnette WN (1981) “Western blotting”: electrophoretic transfer of proteins from sodium dodecyl sulfate polyacrylamide gels to unmodified nitrocellulose and radiographic detection with antibody and radioiodinated protein A. Anal Biochem 112:195–203
Chader GJ, Wiggert B, Lai YL, Lee L, Fletcher RI (1983) Interphotoreceptor retinol-binding protein: a possible role in retinoid transports to the retina. In: Osborne NN, Chader GJ (eds) Progress in retinal research, vol 2. Pergamon Press, Oxford New York, pp 163–189
Chabre M, Applebury ML (1986) Interaction of photoactivated rhodopsin with photoreceptor proteins: the cGMP cascade. In: Stieve H (ed) The molecular mechanism of photoreception. Dahlem Konferenzen 1986. Springer Verlag, Berlin Heidelberg New York Tokyo, pp 51–66
Czerwionka M, Korf HW, Hoffmann O, Busch H, Schachenmayr W (1989) Differentiation in medulloblastomas: correlation between the immunocytochemical demonstration of photoreceptor markers (S-antigen, rod-opsin) and the survival rate in 66 patients. Acta Neuropathol 78:629–636
de Grip WJ (1985) Immunochemistry of rhodopsin. In: Osborne NN, Chader GJ (eds) Progress in retinal research, vol 4. Pergamon Press, Oxford New York, pp 137–180
de Grip WJ (1988) Recent chemical studies related to vision. Photochem Photobiol 48:799–810
de Grip WJ, Daemen FJM, Bonting SL (1980) Isolation and purification of bovine rhodopsin. Methods Enzymol 67:301–320
Donoso LA, Felberg NT, Augsburger JJ, Shields JA (1985) Retina S-antigen and retinoblastoma: a monoclonal antibody and flow cytometric study. Invest Ophthalmol Vis Sci 26:568–572
Foster RG, Timmers AMM, Schalken JJ, de Grip WJ (1989) A comparison of some photoreceptor characteristics in the pineal and retina: II. The Djungarian Hamster (Phodopus sungorus). J Comp Physiol A 165:565–572
Groenendijk GWT, de Grip WJ, Daemen FJM (1979) Identification and characterization of syn- and anti-isomers of retinaloximes. Anal Biochem 99:304–310
Groenendijk GWT, de Grip WJ, Daemen FJM (1980) Quantitative determination of retinals with complete retention of their geometric configuration. Biochim Biophys Acta 617:430–438
Heller J (1975) Interactions of plasma retinol-binding protein with its receptor. Specific binding of bovine and human retinol-binding protein to pigment epithelium cells from bovine eyes. J Biol Chem 250:3613–3619
Korf HW, Møller M, Gery I, Zigler JS, Klein DC (1985a) Immunocytochemical demonstration of retinal S-antigen in the pineal organ of four mammalian species. Cell Tissue Res 239:81–85
Korf HW, Foster RG, Ekström P, Schalken JJ (1985b) Opsinlike immunoreaction in the retinae and pineal organs of four mammalian species. Cell Tissue Res 242:645–648
Korf HW, Klein DC, Zigler JS, Gery I, Schachenmayr W (1986a) S-antigen-like immunoreactivity in a human pineocytoma. Acta Neuropathol (Berl) 69:165–167
Korf HW, Oksche A, Ekström P, van Veen T, Zigler JS, Gery I, Stein P, Klein DC (1986b) S-antigen immunocytochemistry. In: O'Brien P, Klein DC (eds) Pineal and retinal relationships. Academic Press, New York, pp 343–355
Korf HW, Czerwionka M, Reiner J, Schachenmayr W Schalken JJ, de Grip W, Gery I (1987) Immunocytochemical evidence of molecular photoreceptor markers in cerebellar evidence of molecular photoreceptor markers in cerebellar medulloblastomas. Cancer 60:1763–1766
Mirshahi M, Faure JP, Brisson P, Falcon J, Guerlotte J, Collin JP (1984) S-antigen immunoreactivity in retinal rods and cones and pineal photosensitive cells. Biol Cell 52:195–198
Møller M, Glistrup OV, Olsen W (1983) Contrast enhancement of the brownish horseradish peroxidase-activated 3,3′-diaminobenzidine tetrahydrochloride reaction product in black and white photomicrography by the use of interference filters. J Histochem Cytochem 32:37–42
Müller B, Peichl L, de Grip WJ, Gery I, Korf HW (1989) Opsinand S-antigen-like immunoreactions in photoreceptors of the tree shrew retina. Invest Ophthalmol Vis Sci 30:530–535
Papermaster DS (1982) Preparation of antibodies to rhodopsin and the large protein of rod outer segments. Methods Enzymol 81:240–246
Papermaster DS, Converse CA, Zorn M (1976) Biosynthesis and immunocytochemical characterization of a large protein in frog and cattle rod outer segment membranes. Exp Eye Res 23:105–116
Pepperberg DR (1982) Generation of rhodopsin and “artificial” visual pigments in electrophysiologically active photoreceptors. Methods Enzymol 81:452–459
Pepperberg DR, Masland RH (1978) Retinal-induced sensitization of light-adapted rabbit photoreceptors. Brain Res 151:194–200
Pepperberg DR, Lurie M, Brown PK, Dowling JE (1976) Visual adaptation: effects of externally applied retinal on the light-adapted, isolated skate retina. Science 191:394–396
Pepperberg DR, Brown PK, Lurie M, Dowling JE (1978) Visual pigment and photoreceptor sensitivity in the isolated skate retina. J Gen Physiol 71:369–396
Perentes E, Rubinstein LJ, Herman MM, Donoso LA (1986) S-antigen immunoreactivity in human pineal glands and pineal parenchymal tumors. A monoclonal antibody study. Acta Neuropathol (Berl) 71:224–227
Rodrigues MM, Hackett J, Gaskins R, Wiggert B, Lee L, Redmond M, Chader GJ (1986) Interphotoreceptor retinoid-binding protein in retinal rod cells and pineal gland. Invest Ophthalmol Vis Sci 27:844–850
Rohen JW (1964) Das Auge und seine Hilfsorgane. In: v. Möllendorf W, Bargmann W (eds) Handbuch der mikroskopischen Anatomie des Menschen, vol 3, part 4. Springer Verlag, Berlin Göttingen Heidelberg New York, pp 1–662
Rubinstein LJ (1985) Embryonal central neuroepithelial tumors and their differentiating potential. A cytogenic view of a complex neuro-oncological problem. J Neurosurg 62:795–805
Russell DS, Rubinstein LJ (1989) Pathology of tumours of the nervous system, 5th edn. Edward Arnold, London, pp 251–279
Schalken JJ (1987) The visual pigment rhodopsin: immunochemical aspects and induction of experimental autoimmune uveoretinitis. Thesis, University of Nijmegen, Nijmegen
Schalken JJ, de Grip JJ (1986) Enzyme-linked immunosorbent assay for quantitative determination of the visual pigment rhodopsin in total eye extracts. Exp Eye Res 43:431–439
Schalken JJ, Jansen JJM, de Grip WJ, Hawkins RK, Sanyal S (1985) Immunoassay of the rod visual pigment (opsin) in the eyes of rds mutant mice lacking receptor outer segments. Biochim Biophys Acta 839:122–126
Shinohara T, Craft CM, Stein P, Zigler JS, Wistow G, Katial A, Gery I, Klein DC (1986) Isolation of cDNAs for bovine S-antigen. In O'Brien P, Klein DC (eds) Pineal and retinal relationships. Academic Press, Orlando, pp 331–342
Sternberger LA (1986) Immunocytochemistry. John Wiley Sons, New York, pp 1–524
van Veen T, Elofson R, Hartwig JG, Gery I, Mochizuki M, Klein DC (1986) Retinal S-antigen: immunocytochemical and immunochemical studies on the distribution in animal photoreceptors and pineal organs. Exp Biol 45:15–25
Vigh-Teichmann I, Korf HW, Oksche A, Vigh B (1982) Opsin-immunoreactive outer segments and acetylcholinesterase-positive neurons in the pineal complex of Phoxinus phoxinus (Teleostei, Cyprinidae). Cell Tissue Res 227:351–369
Wald G (1968) The molecular basis of visual excitation. Nature 219:800–807
Wiggert B, Chader GJ (1985) Monkey interphotoreceptor retinoid-binding protein (IRBP): isolation, characterization and synthesis. In: Bridges CD, Adler A (eds) The interphotoreceptor matrix in health and disease. Alan R. Liss, New York, pp 89–110
Wurtman RJ, Axelrod J, Kelly DE (1968) The pineal. Academic Press, New York, pp 1–199
Yau KW, Baylor DA (1989) Cyclic GMP-activated conductance of retinal photoreceptor cells. Annu Rev Neurosci 12:289–327
Yoshikami S, Nöll GN (1978) Isolated retinas synthesize visual pigments from retinol congeners delivered by liposomes. Science 200:1393–1395
Zimmerman WF, Lion R, Daemen FJM, Bonting SL (1975) Distribution of specific retinol dehydrogenase activities in subcellular fractions of bovine retina and pigment epithelium. Exp Eye Res 21:325–332
Zimmerman WF, Daemen FJM, Bonting SL (1976) Distribution of enzyme activities in subcellular fractions of bovine retina. J Biol Chem 251:4700–4705
Zülch KJ (1986) Brain tumors. Springer-Verlag, Berlin Heidelberg New York Tokyo, pp 1–704
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Supported by grants from the Deutsche Forschungsgemeinschaft to HWK (Ko 758/3-2) and from NWO-SON (The Netherlands) to WJdG
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Kramm, C.M., Korf, H.W., Czerwionka, M. et al. Photoreceptor differentiation in cerebellar medulloblastoma: evidence for a functional photopigment and authentic S-antigen (arrestin). Acta Neuropathol 81, 296–302 (1991). https://doi.org/10.1007/BF00305871
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DOI: https://doi.org/10.1007/BF00305871