Neuroblastoma cell differentiation

S.K. Sahu, Effects of dexamethasone on neuroblastoma cell differentiation, superoxide dismutase activity, and the possible role of negative oxygen ion on cell differentiation (University Microfilms International) Dissertation 8,012,417 (1979). 

NGF inhibits proliferation and induces differentiation in PC 12 cells (isolated from a pheochromocytoma) and SH-SY5Y cells (isolated from a neuroblastoma [109]. The signal brought by NGF leads to iNOS activation, then to NO-mediated p21 activation [148] following two pathways NGF - iNOS - p53 - p21WAF1 and/or NGF - iNOS - p21WAF1 [109]. Neuroblastoma cell differentiation is induced by TNFa via iNOS expression [149]. 

SK N-SH-SY5Y human neuroblastoma cells differentiated with NGF or undifferentiated (Hongera/-. 2003 ... 

Some neuroblastoma cells overexpress the c-Kit receptor for its ligand, stem cell factor (SCF), and release SCF in an autocrine loop for self-stimulation of mitoses. Imatinib mesylate suppresses PDGF and tyrosine kinase c-Kit (GDI 17) expression. Somatostatin inhibited PDGF-induced phosphorylation of PDGFR and inhibited ras gene amplification. For local invasion, these tumor cells release MMP2/9. The synthetic MMP inhibitor, prinomastat, suppresses MMP production and tumor cell locomotion. However, MMP expression is promotional for neuroblastoma cell differentiation. The presence of MMP is necessary for the neurite formation of retinoic acid-treated neuroblastoma cells neurite formation is the first sign of differentiation induction (vide infra) [1624]. 

Stallings RL, Foley NH, Bray IM, Das S, Buckley PG. MicroRNA and DNA methylation alterations mediating retinoic acid induced neuroblastoma cell differentiation. Semin Cancer Biol. 2011 21 283-90. 

Most recently, a phase-I-study defined a dose of 13-ris-retinoic acid that was tolerable in patients after myeloablative therapy, and a phase-III-trial showed that postconsolidation therapy with 13-cis-retinoic acid improved EFS for patients with high-risk neuroblastoma [7]. Preclinical studies in neuroblastoma indicate that ATRA or 13-cw-RA can antagonize cytotoxic chemotherapy and radiation, such that use of 13-cis-RA in neuroblastoma is limited to maintenance after completion of cytotoxic chemotherapy and radiation. It is likely that recurrent disease seen during or after 13-cis-RA therapy in neuroblastoma is due to tumor cell resistance to retinoid-mediated differentiation induction. Studies in neuroblastoma cell lines resistant to 13-cw-RA and ATRA have shown that they can be sensitive, and in some cases collaterally hypersensitive, to the cytotoxic retinoid fenretinide. Here, fenretinide induces tumor cell cytotoxicity rather than differentiation, acts independently from RA receptors, and in initial phase-I-trials has been well tolerated. Clinical trials of fenretinide, alone and in combination with ceramide modulators, are in development. 

These proteins can be isolated along with taxol-stabilized microtubules (Vallee, 1982), and they appear to be microtubule-assodated proteins which are specific to differentiated neuroblastoma cells (Olmsted and Lyon, 1981). Their role(s) remain to be established... 

The implementation of animal test protocols in the 1980s has been accompanied by the development of a host of alternative methods to study adverse effects of chemicals on reproductive and developmental parameters. For example, rat whole embryo culture stems from the seventies (16), as does the rat limb bud organ culture (17) and rat limb bud and brain micromass was developed in the eighties (18). An elegant nonvertebrate alternative model used regeneration of polyps of Hydra atUnuata from dissociated cells (19). Animal-free in vitro alternatives include those employing the proliferation of a human embryonic palatal mesenchymal cell line (20), the attachment of a mouse ovarian tumor cell line (21), and the differentiation of a neuroblastoma cell line (22) and a embryonal carcinoma cell line (23). Various overviews of methods have been published over the years (24). The predictability of... 

Mummery CL, van den Brink CE, van der Saag PT et al (1984) A short-term screening test for teratogens using differentiating neuroblastoma cells in vitro. Teratology 29(2) 271-279... 

WHO (1993) Guidelines for Drinking Water Quality, 2nd Ed., Vol. 1, Recommendations, Geneva Yoda, K., Shimizu, M. Fujimura, S. (1982) Induction of morphological differentiation in cultured mouse neuroblastoma cells by alkylating agents. Carcinogenesis, 3, 1369-1371... 

Prasad K. N., La Rosa F. G., and Prasad J. E. (1998). Prostaglandins act as neurotoxin for differentiated neuroblastoma cells in culture and increase levels of ubiquitin and beta-amyloid. In Vitro Cell Dev. Biol. Anim 34 265-274. 

For some time, the effects of and responses to vitamin E have been interpreted in terms of an antioxidant mechanism of action. However, several observations have raised the question as to whether other mechanisms could be involved. For example, the effects of selenium and vitamin E on growth and polyunsaturated fatty acid synthesis in cultured mouse fibroblasts could not be reproduced by artificial antioxidants [198, 199]. The specific requirement of (+ )-a-toco-pherol for the phenotypic differentiation of the rotifer [200] may not be through an antioxidant mechanism. The effects of vitamin E on differentiation of neuroblastoma cells [201] and metamorphosis of various species [202] are likely to be due to a growth-factor-like action. A study on the interaction... 

Ellington, J.J., Stancil, F.E., Payne, W.D., Trusty, C.D. (1988) Measurement of Hydrolysis Rate Constants for Evaluation of Hazardous Waste Land Disposal. Volume 3, Data on 70 chemicals. U.S. EPA, EPA-600/3-88/028, NTIS PB 88-234042, Springfield, Virginia. Ellis, P.A., Camper, N.D. (1982) Aerobic degradation of diuron by aquatic microorganisms. J. Environ. Sci. Health B17, 277-290. Erkell, L., Walum, E. (1979) Differentiation of cultured neuroblastoma cells by urea derivatives. Febs Letters 104, 401. 

Oh JE, Karlmark KR, Shin JH, Poliak A, Freilinger A, Hengstschlager M, et al. Differentiation of neuroblastoma cell line N1E-115 involves several signaling cascades. Neuro-chem Res 2005 30(3) 333-348. 

Teojanowski, J. Q., Beodeue, G. M. (2000). Molecular dissection of TrkA signal transduction pathways mediating differentiation in human neuroblastoma cells. Oncogene 19, 2043-2051. 

Kumar, B., Andreatta, C., Koustas, W.T., Cole, W.C., Edwards-Prasad, J., and Prasad, K.N. (2002). Mevastatin induces degeneration and decreases viability of cAMP-induced differentiated neuroblastoma cells in culture by inhibiting proteasome activity, and mevalonic acid lactone prevents these effects. JNeurosci Res 68 627-635. 

Bieberich E, Freischutz B, Suzuki M, Yu RK. Differential effects of glycolipid biosynthesis inhibitors on ceramide-induced cell death in neuroblastoma cells. J. Neurochem. 1999 72 1040-1049. Makino A, Ishii K, Murate M, Hayakawa T, et al. D-threo-1-Phenyl-2-decanoylamino-3-morpholino-l-propanol alters cellular cholesterol homeostasis by modulating the endosome lipid domains. Biochemistry 2006 45 4530-4541. 

Fink CC, Slepchenko B, Moraru n, Watras J, Schaff JC, Loew LM. An image-based model of calcium waves in differentiated neuroblastoma cells. Biophys. J. 2000 79 163-183. 

Fig. 1. Pertussis toxin-mediated ADP ribosylation of membrane G proteins. Isolated cell membranes (50 ng of protein) from N1E 115 cells (mouse neuroblastoma cell line), N2A cells (mouse neuroblastoma cell line), S49-1 eye cells (S49(-) mutated mouse lymphoma cell line deficient in Ga ), 549 wt cells (wild-type mouse lymphoma cell line), RBL (RBL 2H3 rat basophilic leukemia cell line), GH3 cells (GH3 rat hypophyseal tumor cell line), PC-12 (rat pheochromocytoma cell line), HIT-T15 cells (hamster insulinoma cell line), Y-1 cells (mouse adrenal cortex tumor cell line), 108 cc 15 cells (mouse/rat neuroblastoma x glioma hybrid cell line), HL-60 cells (DMSO-differentiated human leukemia cell line), HL-60 (+PT) cells (HL-60 cells pretreated with 25 ng/ml of pertussis toxin for 24 h prior to preparation of membranes), RINm5F cells (rat insulinoma cell line), and C6-2 cells (rat glioma cell line) were subjected to P-ADP-ribosylation as described in section 4.3.3. Samples were precipitated as outlined in section 4.3.5 and subjected to SDS-PAGE with separating gels containing 8% acrylamide (w/v). An autoradiogram of the dried gel is shown. Molecular masses of marker proteins are indicated (kDa). Modified Ga proteins migrate at approximately 40 kDa. Radioactivity running in front of the 30 kDa marker protein comigrates with the dye front...

One study considered the toxicity of aspartame when coadministered with the food colorant Quinoline Yellow (QY). This study showed that synergistic effects were observed when these two additives were given together. Mouse neuroblastoma cells were induced to differentiate and grow neurites when the mixture of aspartame and QY was administered... 

Turkanis SA, Karler R, Partlow LM (1991) Differential effects of delta-9-tetrahydrocanna-binol and its 11-hydroxy metabolite on sodium current in neuroblastoma cells. Brain Res 560 245-250... 

Fig. 5. Induction of poly-iV-acetyllactosamine expression in differentiating mouse neuroblastoma cells. N1E-115 neuroblastoma cells were grown in the undifferentiated form or induced to differentiate by serum starvation for ten days. The glycopeptides metabolically labelled with H-glucosamine were prepared by pronase digestion and fractionated by gel filtration on a column of Bio-Gel P-100. The poIy-fV-acetyllactosamine glycopeptides (poly-LacNAc) were eluted in the fractions indicated by the bar [39].

Worthy of note is an immunohistochemical marker, NB84, that is a monoclonal antibody raised to neuroblastoma cells.Miettinen and coworkers studied 22 cases of undifferentiated neuroblastomas and 83 cases of differentiated neuroblastomas (total of 105 cases) and found that 95.5% of the former and 100% of the latter were positive for NB84. In addition, 4 of 5 (80%) of ES-PNETs and 3 of 3 (100%) of desmoplastic small, round cell tumors also showed positive staining. In contrast, 7 of 39 (17.9%) of ES and 1 of... 

---