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Query: UMLS:C0027819 (neuroblastoma)
 27,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The identification of biologically important and chemically well-defined substances that can promote axon and dendrite formation would improve present understanding of the development of the nervous system. Physiological concentrations of insulin and insulin-like growth factor-II (IGF-II) reversibly enhanced neurite outgrowth (NTO) in human neuroblastoma SH-SY5Y cells cultured in media with and without serum. Nerve growth factor (NGF), in contrast, did not enhance NTO in serum-free media. Furthermore, anti-NGF antiserum inhibited NGF but not insulin-enhanced NTO. Insulin increased [3H]leucine and [3H]uridine uptake. These increases, together with increased NTO, were inhibited by cycloheximide and actinomycin D, respectively. The inhibition of NTO by cycloheximide was reversible. Human neuroblastoma cell lines that were responsive by NTO to NGF were also responsive to insulin, with the exception of line CHP-270. Moreover, cell lines unresponsive by NTO to NGF, and to tumor promoters, were uniformly unresponsive to insulin. These findings suggest that there are common defects in distal sites, because specific NGF and tumor promotor receptors are present in these lines. Insulin increased [3H]thymidine uptake in SH-SY5Y and CHP-100 cells. However, the enhancement of NTO by insulin and IGF-II in SH-SY5Y cells was independent of the cellular proliferation rate. Our results, together with the observations of others, suggest that insulin and IGF-II may modulate NTO in the nervous system.
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PMID:Effects of insulin, insulin-like growth factor-II and nerve growth factor on neurite outgrowth in cultured human neuroblastoma cells. 632 60

Insulin-like growth factor II (IGF-II) acts as an autocrine growth factor for many in vitro tumor cell lines including neuroblastoma. To examine the role of IGF-II in tumor biology we have analyzed a total of 56 primary neuroblastoma tumor samples for the presence of IGF-II using a combination of mRNA and protein analysis. A group of 21 samples was examined for the presence of IGF-II mRNA by slot blot and a separate group of 37 samples was examined for IGF-II immunoreactivity. IGF-II was detected in 48% of the total tumor specimens analyzed. IGF-II immunoreactivity was observed in cells resembling developing neuroblasts and was confined to the cytoplasm and proximal neurites. The appearance of IGF-II mRNA and protein did not correlate with tumor prognostic features including stage, histology, or N-myc amplification. These data suggest that the expression of IGF-II is not confined to a specific stage of the disease but may have a broader role in the pathogenesis of neuroblastoma.
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PMID:Insulin-like growth factor II in the pathogenesis of human neuroblastoma. 749 3

Phorbolester-triggered differentiation of SH-SY5Y neuroblastoma cells requires serum and a prolonged activation of protein kinase C (PKC). Under serum-free conditions development of a mature phenotype requires phorbolester in combination with a member of either the insulin-like growth factor (IGF) or the platelet-derived growth factor family. Here we report that basic and acidic fibroblast growth factor (FGF) and epidermal growth factor, but not nerve growth factor, synergistically potentiate phorbolester-induced differentiation. Alone these factors induced a mitogenic response which varied in magnitude, with basic FGF and IGF-I being the two most potent mitogens. However, a combination of basic FGF and IGF-I induced differentiation as judged by morphology and the increase in growth associated protein (GAP-43) and neuropeptide tyrosine mRNA levels. In contrast to the phenotype obtained in the presence of phorbolester, bFGF and IGF-I-treated SH-SY5Y cells retained their capacity to proliferate. Finally, in these cells, the phosphorylation of the endogenous PKC substrate, myristoylated alanine-rich C-kinase substrate (MARCKS), was slightly increased during several days, suggesting an involvement of PKC in the bFGF and IGF-I-induced differentiation.
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PMID:Basic FGF and IGF-I promote differentiation of human SH-SY5Y neuroblastoma cells in culture. 751 11

Hypoglycemia occurred in a 2-year-old girl with neuroblastoma. Initially, growth hormone secretion was suppressed, and she had low levels of insulin-like growth factor (IGF)-I and IGF binding protein-3, but elevated levels of large molecular weight IGF-II. We postulated that the pathogenesis of her hypoglycemia involved production of IGF-II by her neuroblastoma, leading to GH suppression and an abnormally elevated ratio of IGF to IGF binding protein. She was successfully treated with growth hormone; treatment was associated with normalization of the growth hormone-dependent growth factor levels and with euglycemia.
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PMID:Non-islet-cell tumor associated with hypoglycemia in a child: successful long-term therapy with growth hormone. 765 70

Insulin-like growth factor II (IGF-II) is implicated in the development of the vertebrate neural circuitry, and increases neurite growth in vitro and in vivo. We examined the relationship of IGF-II expression to the in vitro differentiation induced by retinoic acid (RA). We find that RA stimulates an increase in IGF-II messenger RNA (mRNA) in the SK-N-SH (SH) neuroblastoma cell line. An increase of IGF-II mRNA is detected within 12 h of treatment and precedes morphological differentiation. A RA dose response test indicates that an increase in IGF-II mRNA occurs within 2 days in SH cells treated with doses of RA from 1 x 10(-8) to 1 x 10(-5) M. We suggest that IGF-II expression may be regulated either directly or indirectly by RA in vitro and may lead to neuroblastoma differentiation.
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PMID:Retinoic acid induces insulin-like growth factor II expression in a neuroblastoma cell line. 836 91

Autocrine stimulation of the type I insulin-like growth factor receptor (IGF-IR) by IGF-II is one mechanism that allows cancer cells to maintain unregulated growth and to resist programmed cell death (PCD). SH-SY5Y and SHEP cells are cloned human neuroblastoma (NBL) lines originating from a single primary tumor. SH-SY5Y cells, which express abundant cell surface IGF-IR and produce IGF-II, exhibit serum independent growth and resist PCD due to hypoxia and hyperosmolar conditions. In contrast, SHEP cells, which produce no IGF-II and express five-fold fewer IGF-IRs, die in serum-free media or following exposure to metabolic stressors. To better understand the roles of IGF-IR and its ligand, IGF-II, in NBL carcinogenesis, we stably transfected SHEP cells with either IGF-II or IGF-IR. Unregulated expression of IGF-II did not alter the growth characteristics of SHEP/human IGF-II transfectants. In contrast, overexpression of IGF-IR allowed SHEP/IGF-IR transfectants to survive in media supplemented only by IGF-II. IGF-IR abundance correlated in a graded fashion with resistance to PCD in response to three different death-inducing paradigms: mitogen withdrawal, hyperosmolar metabolic stress, and treatment with etoposide. Our results suggest that adjuvant therapy aimed at reducing IGF-IR abundance may enhance chemotherapy-coupled apoptosis in the treatment of NBL.
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PMID:Insulin-like growth factor I receptor prevents apoptosis and enhances neuroblastoma tumorigenesis. 881 51

Somatostatin possesses antisecretory and antiproliferative activity on some human tumors. We herein report that, in a human neuroblastoma cell line, the somatostatin analogue BIM 23014 inhibited mitogen-activated protein (MAP) kinase activity stimulated by either insulin-like growth factor-1, whose receptor bears a tyrosine kinase, or carbachol, which acts at a G-protein coupled receptor. In a human small cell lung carcinoma line BIM inhibited serum-stimulated MAP kinase activation. These inhibitory actions occur in a dose range quite similar to that observed for suppression of proliferation induced by the analogue in the same cell lines. The decrease in cAMP elicited by the analogue in the two cell lines is not responsible for its inhibitory action on MAP kinase and cell growth. Moreover, the analogue did not modify intracellular [Ca2+] and pH. An involvement of a phosphatase activity is suggested.
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PMID:A somatostatin analogue inhibits MAP kinase activation and cell proliferation in human neuroblastoma and in human small cell lung carcinoma cell lines. 895 39

Neuroblastoma is an embryonal tumor derived from the sympathetic nervous system. Although all neuroblastomas have a neuronal character, a subset of tumors also show evidence of extra-adrenal neuroendocrine differentiation in discrete cell layers. A characterization of the cells of the developing human sympathetic nervous system was performed, identifying growth-associated protein-43, neuropeptide tyrosine, and Bcl-2 as marker genes for sympathetic neurons. Whereas all neuroblastomas express growth-associated protein-43, neuropeptide tyrosine, and Bcl-2, tumors with differentiating cells with neuroendocrine features expressed these genes only in the morphologically immature, proliferating cells. Thus, with neuroendocrine tumor cell differentiation, neuronal marker gene expression vanished and proliferation ceased and was succeeded by expression of chromogranin A/B and insulin-like growth factor-2, markers of neuroendocrine chromaffin differentiation. These tumors appear to provide examples of spontaneous lineage conversion from a neuronal to a neuroendocrine phenotype.
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PMID:In vivo spontaneous neuronal to neuroendocrine lineage conversion in a subset of neuroblastomas. 900 28

Neuroblastoma is, at the same time, the most common and the most puzzling extracranial solid tumour in childhood, being able to regress spontaneously despite widespread dissemination, showing a striking high incidence of the in situ form, and, finally, being resistant even to aggressive chemotherapy. The reasons of this bizarre behaviour are still largely unknown due to our little knowledge of neuroblastoma pathophysiology. There is increasing body of evidence that the insulin-like growth factor system plays a crucial role in the proliferation and differentiation of neuroblastoma cells and it is conceivable that a better knowledge of this role might potentially lead to new and more effective therapeutic strategies. Here we review the most recent insights into the biology of neuroblastoma, focusing on the close links with the insulin-like growth factor system and the potential clinical perspectives.
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PMID:Neuroblastoma and insulin-like growth factor system. New insights and clinical perspectives. 912 6

With respect to a potential role for CD44 in neuronal tumors, we investigated the regulation of variant CD44 exon containing isoforms (CD44V) in the human neuroblastoma cell line SK-N-SH in response to treatment with differentiation-inducing and mitogenic factors. While the standard form of CD44 was expressed at high levels in both treated and untreated cells, variant isoforms were strongly upregulated in response to treatment with 12-O-tetradecanoyl phorbol-13-acetate (TPA), insulin-like growth factor-1 (IGF-1) and platelet-derived growth factor (PDGF) as shown by RT-PCR and immunofluorescence. One of the CD44 isoforms contains sequences encoded by variant exon v6 (CD44V6), which was originally described as a metastasis-associated antigen. Using specific inhibitors, we explored the signal transduction pathways involved in the expression of variant CD44. GF-109203X, a specific inhibitor of protein kinase C effectively blocked TPA- and IGF-1-upregulated expression of CD44v6. Wortmannin, a specific inhibitor of phosphoinositide 3-kinase (PI 3-kinase) partly reduced IGF-1 and PDGF induced CD44v6 expression. The induction of CD44V by TPA, IGF-1 or PDGF was correlated with an increased cellular binding to hyaluronic acid, a major counterreceptor for CD44. The increased binding caused by TPA or IGF-1 could specifically be blocked by the above inhibitors. Thus, PKC and PI 3-kinase are likely to transduce growth factor induced signals that upregulate specific CD44 splice variants.
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PMID:Expression of CD44 isoforms in neuroblastoma cells is regulated by PI 3-kinase and protein kinase C. 919 Aug 98


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