Phenotypic changes of human neuroblastoma cells in culture induced by 12‐<i>O</i>‐tetradecanoyl‐phorbol‐13‐acetate

Påhlman, Sven; Odelstad, Lena; Larsson, Erik; Grotte, G.; Nilsson, Kenneth

doi:10.1002/ijc.2910280509

Cited by 231 publications

(117 citation statements)

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“…The latter observation led to the early utilization of urinary catecholamine metabolites in the diagnosis of neuroblastoma (4). The finding that some human neuroblastoma cell lines have the capacity to differentiate into a more mature sympathetic differentiation stage by phorbolester (5) and retinoic acid (6, 7) treatments, together with similar observations in hematopoietic tumor cell lines, established the concept of tumor cell differentiation and in vitro model systems to study this phenomenon (reviewed in (8)). …”

Section: Neuroblastoma -A Model Of Tumor Cell Differentiationmentioning

confidence: 90%

Neuroblastoma aggressiveness in relation to sympathetic neuronal differentiation stage

Mohlin

Wigerup

Påhlman

2011

Seminars in Cancer Biology

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Neuroblastoma aggressiveness in relation to sympathetic neuronal differentiation stage.Mohlin, Sofie; Wigerup, Caroline; Påhlman, Sven Link to publication Citation for published version (APA): Mohlin, S., Wigerup, C., & Påhlman, S. (2011). Neuroblastoma aggressiveness in relation to sympathetic neuronal differentiation stage. Seminars in Cancer Biology, 21(4), 276-282. DOI: 10.1016276-282. DOI: 10. /j.semcancer.2011 General rights Copyright and moral rights for the publications made accessible in the public portal are retained by the authors and/or other copyright owners and it is a condition of accessing publications that users recognise and abide by the legal requirements associated with these rights.• Users may download and print one copy of any publication from the public portal for the purpose of private study or research.• You may not further distribute the material or use it for any profit-making activity or commercial gain • You may freely distribute the URL identifying the publication in the public portal Neural crest and development of the sympathetic nervous systemThe sympathetic nervous system (SNS) originates from the neural crest, an ephemeral structure during vertebrate development. Located along the neural fold, cells on the neural tube in the ectoderm give rise to the neural crest, in turn generating different derivatives, such as the cranial, hindbrain, vagal and trunk neural crest (reviewed in (9)). Trunk neural crest cells migrate from the neural tube along two defined routes, with one group of cells migrating early along a ventral pathway, giving rise to glial cells and neurons, whereas a later migrating group of cells follows a lateral pathway and gives rise to melanocytes in the skin (10, 11). These mutations were rare in all four studies indicating locus heterogeneity for predisposition of inherited disease, but still demonstrated the importance of the PHOX2B gene in neuroblastoma oncogenesis and initiation (Fig. 1) (58), and Fig. 1). Neuroblastoma differentiation stage and clinical outcomeThere is a well-documented difference in aggressive behavior between the morphologically undifferentiated (neuroblastoma proper) and the differentiated (ganglioneuroblastoma, Cellular adaptation to hypoxiaThe biological consequences of hypoxia involve induced angiogenesis, a switch in glucose metabolism and increased invasion and migration capacities, changes that stimulate tumor progression. The hypoxic response is mainly mediated by stabilization of the hypoxia inducible factor (HIF) proteins. HIFs are heterodimeric transcription factors composed of an oxygen sensitive  subunit and a constitutively expressed  subunit. At physiological oxygen levels, the  subunit is hydroxylated by the oxygen-dependent prolyl hydroxylases (PHDs), leading to interaction with the von Hippel Lindau-ubiquitin ligase complex, followed by ubiquitination and proteasomal degradation. At hypoxia, the PHDs are inactive leading to the 9 stabilization of the HIF- subunits, and by dimerization with the  subunit the comple...

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Section: Neuroblastoma -A Model Of Tumor Cell Differentiationmentioning

confidence: 90%

Neuroblastoma aggressiveness in relation to sympathetic neuronal differentiation stage

Mohlin

Wigerup

Påhlman

2011

Seminars in Cancer Biology

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“…In the epithelial cell lines used in this study, the main type of FPMM was ruffling. The phorbol ester tumor promoter TPA is known to induce ruff ling in several epithelial cell lines (6,10,16,18,19) as EGF does in A431 cells (4). Here we objectified this effect for TPA on MCF-7/AZ cells and for EGF on A431 cells.…”

Section: Discussionmentioning

confidence: 99%

Simple method for quantification of fast plasma membrane movements

1992

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We present a method for the quantification of the fast plasma membrane movements that are involved in ruffling, blebbing, fast shape change, and fast translocation. The method is based on the Kontron Vidas image analysis computer program. Video images from cells viewed through an inverted microscope were transmitted to the computer. The procedure was as follows: 4 consecutive video images were averaged (imagel); 28 s later a second set of 4 video images was averaged (image 2); image 2 was subtracted from image 1 and the grey level of each pixel of the resulting image was increased with 128 grey level units, resulting in the subtraction image, showing a uniform grey background speckled with brighter and darker spots corresponding to areas of movement. These spots were discriminated and turned into white objects against a black background. Interactive editing was used to delete artefacts that resulted from floating debris. The total area of the discriminated objects was measured, and the parameter motile area in pm2 per cell was calculated. We have applied our method to the study of motility induced in epithelial cell lines by the tumor promoter 12-0-tetradecanoyl-phorbol-13-acetate and by epidermal growth factor.Key terms: Cell motility, cell membrane, cell-surface, ruffling, blebbing, cellshape, translocation, image analysis, TPA, EGF Direct analysis of cell motility in vivo is problematic because of the lack of transparency of three-dimensional living tissues. There is evidence indicating that the study of cell motility on a flat surface in vitro is relevant for the situation in vivo because cells have an inherent motility program (11,12,21). Various aspects of cell motility (see Methods for terminology used in this paper) can be assessed in vitro. Several methods have been described to quantify translocation (7,15,23), directional migration including chemokinesis and chemotaxis (13,251, as well as shape change (17,24). Quantification of fast plasma membrane movements involved in ruffling, blebbing, formation or movement of cytopodia, and fast shape change or fast translocation has received less attention. Partin et al. (17) have described an elaborate Fourier analysis for quantification of the various aspects of cell motility, including ruffling. Recently Tatsuka et al. (22) described a method for quantification of "momentary alterations of cell shape" reflecting ruff ling, pseudopodal activity, and fast cell translocation, using automatic image analysis on Allen video-enhanced contrast-differential interference contrast images. Here, we report on a simple and rapid method for quantification of fast plasma membrane movements. It is entirely based on the Vidas automatic grey level image analysis program that is commercially available from Kontron (Eching, West Germany). We have tested our method on cell cultures differing in their type or intensity of motility as estimated from time-lapse video films. As an application of our method we analysed the effect of the tumor promoter 12-0-tetradecanoyl-phorbol-13-acet...

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“…6, 3), as reported previously. 17,19,20 Cells stimulated with the combination of RAϩIFN-␥ differed from both RA and IFN-␥-stimulated cells; they were often large, spread out, flattened cells, in contrast to the smaller RA-differentiated cells, and extended rather thick and less branched processes compared to the IFN-␥-treated cells (Fig. 6b-d).…”

Section: Ifn-␥ Cooperates With Ra and Tpa To Induce Differentiation Omentioning

confidence: 99%

“…The percentage of morphologically differentiated cells was determined by counting at least 100 randomly chosen cells, where cells exhibiting neurites Ն 50 m were scored as positive. 19 The neurite outgrowth index was calculated as the product of the percentage of cells with neurites and the average total neurite length per cell. 20 …”

Section: Cell Cultures and Induction Of Differentiationmentioning

confidence: 99%

“…Treatment of neuroblastoma cell lines, including many with amplified N-myc genes, with agents such as retinoic acid (RA), 16 -18 phorbol ester, 19,20 dibutyryl c-AMP 21 and interferon-␥ (IFN-␥) [22][23][24][25][26] in vitro lead to various levels of morphological and biochemical neuronal differentiation linked to growth inhibition. The differentiation is accompanied by reduction of N-myc expression.…”

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Interferon-? cooperates with retinoic acid and phorbol ester to induce differentiation and growth inhibition of human neuroblastoma cells

et al. 2001

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The prognosis of patients with advanced stages of neuroblastoma with N-myc amplification remains poor despite escalated therapy, a situation that has called for alternative therapeutic approaches. Neuroblastoma cells, which represent immature peripheral neuronal cells, treated with certain physiologic and nonphysiologic agents such as retinoic acid (RA), phorbol esters and interferons (IFN) in vitro undergo cellular differentiation and stop to divide, a process that mimics normal neuronal development. Such "differentiation therapy" using RA after autologous bone marrow transplantation has recently given encouraging results in neuroblastoma patients with advanced disease. Considering approaches for improved differentiation therapy, we investi-

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Phenotypic changes of human neuroblastoma cells in culture induced by 12‐O‐tetradecanoyl‐phorbol‐13‐acetate

Cited by 231 publications

References 27 publications

Neuroblastoma aggressiveness in relation to sympathetic neuronal differentiation stage

Neuroblastoma aggressiveness in relation to sympathetic neuronal differentiation stage

Simple method for quantification of fast plasma membrane movements

Interferon-? cooperates with retinoic acid and phorbol ester to induce differentiation and growth inhibition of human neuroblastoma cells

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