Summary
The role of nerve growth factor (NGF) in the development, maintenance and regeneration of the mammalian sensory and sympathetic nervous systems has been well characterized, as has the ability of NGF to induce a variety of neoplastic cell lines of nuroectodermal (neurogenic) origin to differentiate. The ability to stimulate neoplastic cells of neurogenic origin to differentiate suggests that NGF may prove useful as a reverse transforming agent for the treatment of neurogenic tumors. Five human neurogenic tumor cell lines were evaluated for their response to NGF in vitro to determine whether the NGF is capable of inducing changes consistent with a reverse transforming response. Results indicate that NGF was able to reverse some of the transformed properties of these tumor cell lines, as NGF treatment stimulated neoplastic cells to develop a more differentiated phenotype, diminished or arrested growth, and induced changes that were persistent.
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Azar CG, Scavarda NJ, Reynolds CP, Brodeur GM (1990) Multiple defects of the nerve growth factor receptor in human neuroblastomas. Cell Growth Different 1:421–428
Buxser S, Decker D, Ruppel P (1990) Relationship among types of nerve growth factor receptors on PC12 cells. J Biol Chem 265:12701–12710
Burmeister DW, Lyser K (1982) Process formation in the human neuroblastoma clone SK-N-SH-SY5Y in vitro. Diss Abstr Int 43:1334-B
Dichter MA, Tischler AS, Greene LA (1977) Nerve growth factor induced increase in electrical excitability and acetylcholine sensitivity of a rat pheochromocytoma cell line. Nature 268:501–504
Doherty P, Seaton P, Flanigan TP, Walsh FS (1988) Factors controlling the expression of the nerve growth factor receptor in PC12 cells. Neurosci Lett 92:222–227
Fabricant RN, De Larco JE, Todaro GJ (1977) Nerve growth factor receptors on human melanoma cells in culture. Proc Natl Acad Sci USA 74:565–569
Gerschenson M, Graves K, Carson SD, Wells RS, Pierce GB (1986) Regulation of melanoma by the embryonic skin. Proc Natl Acad Sci USA 83:7307–7310
Green SH, Greene LA (1986) A single Mr=103,000 125I-B-nerve growth factor-affinity-labeled species represents both the low and high affinity forms of the nerve growth factor receptor. J Biol Chem 261:15316–15326
Greene LA, Rein G (1977) Release, storage and uptake of catecholamines by a clonal cell line of NGF responsive pheochromocytoma cells. Brain Res 129:247–263
Greene LA, Tischler AS (1976) Establishment of a noradrenergic clonal line of rat adrenal pheochromocytoma cells which respond to nerve growth factor. Proc Natl Acad Sci USA 73:2424–2428
Hempstead BL, Schleifer LS, Chao MV (1989) Expression of functional nerve growth factor receptors after gene transfer. Science 243:373–375
Hempstead BL, Martin-Zanca D, Kaplan DR, Parada LF, Chao MV (1991) High-affinity NGF binding requires coexpression of the trk proto-oncogene and the low affinity NGF receptor. Nature 350:678–683
Jensen LM (1987) Phenotypic differentiation of aphidicolin-selected human neuroblastoma ciltures after long-term exposure to nerve growth factor. Dev Biol 120:56–64
Korshing S, Thoenen H (1983) Nerve growth factor in sympathetic ganglia and corresponding target organs of the rat: correlation with density of sympathetic innervation. Proc Natl Acad Sci USA 80:3513–3516
Kumar S, Huber J, Pena LA, Perez-Polo JR, Werrbach-Perez K, de Villis J (1990) Characterization of functional nerve growth factor-receptors in a CNS glial cell line: monoclonal antibody 217c recognizes the nerve growth factor-receptor on C6 glioma cells. J Neurosci Res 27:408–417
Kuramoto T, Werrbach-Perez K, Perez-Polo JR, Haber B (1981) Membrane properties of a human neuroblastoma II. Effects of differentiation. J Neurosci Res 6:441–449
Landreth GE, Shooter EM (1980) Nerve growth factor receptors on PC12 cells: ligand-induced conversion from lowto high-affinity states. Proc Natl Acad Sci USA 77:4751–4755
Lazarovici P, Dickens G, Kuzuya H, Guroff G (1987) Longterm heterologous down-regulation of the epidermal growth factor receptor in PC12 cells by nerve growth factor. J Cell Biol 104:1611–1621
Levi A, Shechter Y, Neufeld EJ, Schlessinger J (1980) Mobility, clustering, and transport of nerve growth factor in embryonal sensory cells and in a sympathetic neuronal cell line. Proc Natl Acad Asci USA 77:3469–3473
Levi-Montalcini R (1987) Nerve growth factor 35 years later. Science 237:1154–1162
Levi-Montalcini R, Aloe L (1985) Differentiating effects of murine nerve growth factor in the peripheral and central nervous systems of Xenopus laevis tadpoles. Proc Natl Acad Sci USA 82:7111–7115
Martinez HJ, Dreyfus CF, Jonakait GM, Black IB (1985) Nerve growth factor promotes cholinergic development in brain striatal cultures. Proc Natl Acad Sci USA 82:7777–7781
Marushige Y, Raju NR, Marushige K, Koestner A (1987) Modulation of growth and of morphological characteristics in glioma cells by nerve growth factor and glia maturation factor. Cancer Res 47:4109–4115
Marushige Y, Marushige K, Koestner A (1989) Chemical control of growth and morphological characteristics of anaplastic glioma cewlls. Anticancer Res 9:1729–1736
Matsushima H, Bogenmann E (1990) Nerve growth factor induces neuronal differentiation in neuroblastoma cells transfected with the NGF receptor cDNA. Mol Cell Biol 10:5015–5020
Perez-Polo JR, Werrbach-Perez K, Tiffany-Castiglioni E (1979) A human clonal cell line model of differentiating neurons. Dev Biol 71:341–355
Perez-Polo JR, Reynolds CP, Tiffany-Castiglioni E, Ziegler M, Schulze I, Werrback-Perez K (1982) NGF effects on human neuroblastoma lines: a model system. Proteins in the nervous system: structure and function. Alan R. Liss, New York, pp285–299
Podesta AH, Mullins J, Pierce GB, Wells RS (1984) The neurula stage mouse embryo in control of neuroblastoma. Proc Natl Acad Sci USA 81:7608–7611
Raju NR, Koestner A, Marushige K, Lovell KL, Okazaki D (1989) Effect of nerve growth factor on the transplacental induction of neurinomas by ethylnitrosourea in Sprague-Dawley rats. Cancer Res 49:7120–7123
Reed JK, England D (1986) The effect of nerve growth factor on the development of sodium channels in PC12 cells. Biochem Cell Biol 64:1153–1159
Reynolds CP, Perez-Polo JR (1975) Human neuroblastoma: glial induced morphological differentiation. Neurosci Lett 1:91–97
Reynolds CP, Perez-Polo JR (1981) Induction of neurite outgrowth in the IMR-32 human euroblastoma cell line by nerve growth factor. J Neurosci Res 6:319–325
Ross AH, Grob P, Bothwell M, Elder DE, Ernst CS, Marano N, Ghrist BFD, Slemp CC, Herlyn M, Aikinson B, Koprowski H (1984) Characterization of nerve growth factor receptor in neural crest tumors using monoclonal antibodies. Proc Natl Acad Sci USA 81:6681–6685
Rudy B, Kirschenbaum B, Greene LA (1982) Nerve growth factor-induced increase in saxitoxin binding to rat PC12 pheochromocytome cells. J Neurosci 2:1405–1411
Schubert D, Whitlock C (1977) Alteration of cellular adhesion by nerve growth factor. Proc Natl Acad Sci USA 74:4055–4058
Schubert D, Hienenmann S, Kidakoro Y (1977) Cholinergic metabolism and synapse formation by a rat nerve cell line. Proc Natl Acad Sci USA 74:2579–2583
Sonnenfeld KH, Ishii DN (1982) Nerve growth factor effects and receptors in cultured human neuroblastoma cell lines. J Neurosci Res 8:375–391
Sonnenfeld KH, Ishii DN (1985) Fast and slow nerve growth factor binding sites in human neuroblastoma and rat pheochromocytoma cell lines: relationship of site to each other and to neurite formation. J Neurosci 5:1717–1728
Tischler AS, Greene LA (1978) Morphologic and cytochemical properties of clonal rat pheochromocytoma cells which respond to nerve growth factor. Lab Invest 39:77–89
Vale RD, Shooter EM (1985) Assaying binding of nerve growth factor to cell surface receptors. Methods Enzymol 109:21–39
Vinores SA, Koestner A (1980) The effect of nerve growth factor on undifferentiated glioma cells. Cancer Lett 10:309–318
Vinores SA, Koestner A (1981) Effect of nerve growth factor producing cells on anaplastic glioma and pheochromocytoma clones: involvement of other factors. J Neurosci Res 6:389–401
Waris T, Rechardt L, Waris P (1973) Differentiation of neuroblastoma cells induced by nerve growth factor in vitro. Experientia 29:1128–1129
Welcher AA, Bitler CM, Radeke MJ, Shooter EM (1991) Nerve growth factor binding domain of the nerve growth factor receptor. Proc Natl Acad Sci USA 88:159–163
Yanker BA, Shooter EM (1982) The biology and mechanism of action of nerve growth factor. Annu Rev Biochem 51:845–868
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Supported by NIH grant CA32594, an NIH Post Doctoral Fellowship to Dr. Yaeger, a grant from the Preuss Foundation and a BRSG grant (College of Veterinary Medicine, Michigan State University)
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Yaeger, M.J., Koestner, A., Marushige, K. et al. The reverse transforming effects of nerve growth factor on five human neurogenic tumor cell lines: in vitro results. Acta Neuropathol 83, 72–80 (1991). https://doi.org/10.1007/BF00294433
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DOI: https://doi.org/10.1007/BF00294433