bFGF Induces Differentiation and Death of Olfactory Neuroblastoma Cells (original) (raw)
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Induction of differentiation of human olfactory neuroblastoma cells into odorant-responsive cells
Neuroscience, 1996
Olfactory neuroblastoma is a rare malignancy of the olfactory mucosa that may be derived from the olfactory epithelium. To characterize this tumor, we cultured olfactory neuroblastoma cells in the presence or absence of growth factors (transforming growth factor α and basic fibroblast growth factor) known to affect olfactory tissue and assessed their responsiveness to known odorants by measuring changes in intracellular calcium. Untreated cells did not respond to odorants. Basic fibroblast growth factor treatment had cytotoxic effects, and treated cells did not respond to odorants. Transforming growth factor α treatment resulted in the induction of odor responsiveness in these cells. Cells responded to odorants at 100 nM to 100 μM concentrations and responded with both increases and decreases in intracellular calcium. Increases in intracellular calcium were mediated by a calcium influx and were reversibly blocked by compounds known to inhibit second messenger pathways in olfactory receptor neurons. The calcium responses of the olfactory neuroblastoma cells were thus specific to the odorants and similar to those found in olfactory receptor neurons.The results support the notion that olfactory neuroblastoma cells may be of olfactory origin and thus they can be used as a model cell line to study human olfaction.
The OP27 cell line as a model system to study the effects of FGF-2 in olfactory neuronal development
2004
Due to its unique capacity to regenerate continously, the olfactory neuroepithelium serves as an excellent model system for investigating the molecular and cellular mechanisms involved in neurogenesis. The OP27 cell line (generated by infecting embryonic mouse olfactory placodes with a retrovirus carrying the temperature-sensitive alleles of the SV 40 large T antigen) was used as an in vitro system to test the effects of fibroblast growth factor-2 (FGF-2) in directing olfactory neurogeneslS. The OP27 cells proliferate under the control of the retrovirus at the permissive temperature (33°C). When shifted to the non-permissive temperature (39°C) the SV40 large T antigen is inactivated and the cells stop dividing, thereby allowing one to study the effects of growth factors on these cells. Although FGF-2 also plays an important role in regulating the proliferation of neural progenitors, the main focus in this study was its effect on neuronal differentiation When shifted to 39°C in the p...
Odorant receptor genes are expressed in olfactory neuroblastoma
Genetics and Molecular Research, 2013
Olfactory neuroblastoma (ONB) is a malignant tumor found in the human nasal cavity. These tumors are rare and poorly characterized at the molecular level. In this study, we asked whether olfactory-specific genes are expressed in ONBs by using reversetranscriptase-polymerase chain reaction. We found that the olfactory marker protein and the RIC-8B genes, which are specifically expressed in mature olfactory neurons, are expressed in ONBs. Importantly, we also found that ONBs express a large variety of odorant receptor genes, representative of different odorant receptor gene subfamilies. Our results show that the ONBs express genes that are normally expressed in mature olfactory neurons and indicate that they are derived from progenitor or immature cells in the olfactory epithelium and not from a clonal expansion of a single or few mature olfactory neurons.
Brain Research, 2002
Numerous in vitro studies of neurogenesis of olfactory receptor neurons (ORNs) suggest that transforming growth factor (TGF)-β promotes the maturation/differentiation of olfactory progenitors. We demonstrate that in vivo both mature and immature ORNs, and possibly a basal neuronal progenitor cell, express the TGF-β type II receptor (TGF-βRII), suggesting that these cells are targets for TGF-β signaling. In a previous study
Cancers, 2021
Simple Summary The gene expression profile of ONB defines a group of patients with a dismal prognosis and identifies potentially targetable pathways. Better prognostic stratification may offer new tailored approaches for the treatment and follow-up of ONB. The integration of new therapeutic agents with standard surgical and RT strategies may improve the outcomes in cases with worse prognoses. Furthermore, the ontogenesis of ONB in basal and neural subtypes is mirrored by different transcriptional pathways, paving the way towards different therapeutic approaches. Abstract Olfactory neuroblastoma (ONB) is a rare sinonasal neoplasm with a peculiar behavior, for which limited prognostic factors are available. Herein, we investigate the transcriptional pathways altered in ONB and correlate them with pathological features and clinical outcomes. We analyze 32 ONB patients treated with curative intent at two independent institutions from 2001 to 2019 for whom there is available pathologic a...
Neuron, 1994
Olfactory receptor neurons are produced continuously in mammalian olfactory epithelium in vivo, but in explant cultures neurogenesis ceases abruptly. We show that in vitro neurogenesis is prolonged by fibroblast growth factors (FCFs), which act in two ways. FGFs increase the likelihood that immediate neuronal precursors (INPs) divide twice, rather than once, before generating neurons; this action requires exposure of INPs to FCFs by early Gl. FGFs also cause a distinct subpopulation of explants to generate large numbers of neurons continually for at least several days. The data suggest that FGFs delay differentiation of a committed neuronal transit amplifying cell (the INP) and support proliferation or survival of a rare cell, possibly a stem cell, that acts as a progenitor to INPs.
Glia, 2002
Olfactory ensheathing cells can develop into distinct subtypes in culture after incubation in serum-free medium conditioned by astrocytes, which have Schwann cell-like and astrocyte-like properties. It has not been possible so far to modulate and grow large numbers of these olfactory ensheathing cell subtypes. In this study, we have shown that astrocyte-conditioned medium, although promoting differentiation of the two olfactory ensheathing cell types, is growth-restrictive after 14 days, probably due to the upregulation of p16 and p27. Growth arrest can be overridden and cells maintained for a further 11 weeks, by a mitogen mix of fibroblast growth factor 2, forskolin, and heregulin (olfactory mitogen medium) combined with astrocyte-conditioned medium. In the absence of astrocyte-conditioned medium, combinations of the same factors can also override growth arrest but to a lesser extent. Olfactory mitogen medium combined with astrocyte-conditioned medium upregulates O4 and low-affinity nerve growth factor receptor expression on olfactory ensheathing cells, leading to a 100% Schwann cell-like phenotype. If cells are maintained in olfactory mitogen medium alone, or if they are treated with forskolin or fibroblast growth factor 2 diluted in serum-free medium, O4 and lowaffinity nerve growth factor receptor expression remains at 100%, but there is also an increase in expression of E-NCAM, the astrocyte-like marker. Medium containing serum also overrides growth arrest, but for only 4 weeks, during which time most differentiation-specific markers disappear. These studies have allowed us to define conditions to modulate the olfactory ensheathing cell phenotype. GLIA 37: 349 -364, 2002.
Molecular Brain Research, 2001
In the primary olfactory pathway axons of olfactory neurons (ONs) are accompanied by ensheathing cells (ECs) as the fibres course towards the olfactory bulb. Ensheathing cells are thought to play an important role in promoting and guiding olfactory axons to their appropriate target. In recent years, studies have shown that transplants of ECs into lesions in the central nervous system (CNS) are able to stimulate the growth ofaxons and in some cases restore functional connections. In an attempt to identify a possible mechanism underlying EC support for olfactory nerve growth and CNS axonal regeneration, this study investigated the production of growth factors and expression of corresponding receptors by these cells. Three techniques immunohistochemistry, enzyme linked immunosorbent assay (ELISA) and reverse transcriptase-polymerase chain reaction (RT-PCR) were used to assess growth factor expression in cultured ECs. Immunohistochemistry showed that ECs expressed nerve growth factor (NGF), brain derived neurotrophic factor (BDNF) and glial cell-line derived neurotrophic factor (GDNF). ELISA confirmed the intracellular presence of NGF and BDNF and showed that, compared to BDNF, about seven times as much NGF was secreted by ECs. RT-PCR analysis demonstrated expression of mRNA for NGF, BDNF, GDNF and neurturin (NTN). In addition, ECs also expressed the receptors trkB, GFRa-1 and GFRa-2. The results of the experiments show that ECs express a number of growth factors and that BDNF in particular could act both in a paracrine and autocrine manner.