Differential Effects of Neuropeptide Y on the Growth and Vascularization of Neural Crest–Derived Tumors

Kitlińska, Joanna; Abe, Ken; Kuo, Lydia E; Pons, Jennifer; Yu, Muchieh; Li, Lijun; Tilan, Jason U.; Everhart, Lindsay M.; Lee, Edward W.; Żukowska, Zofia; Toretsky, Jeffrey A.

doi:10.1158/0008-5472.can-04-2192

Cited by 127 publications

(230 citation statements)

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“…The high expression of its gene in pheochromocytoma may participate to the excessive secretion of catecholamines observed in these tumors through an autocrine effect of the peptide. Because NPY failed to alter rat PC12 cell proliferation or apoptosis (Kitlinska et al 2005), it is unlikely that this peptide participates to pheochromocytoma cell transformation.…”

Section: Discussionmentioning

confidence: 96%

“…Several reports have described the occurrence of NPY and its receptors in pheochromocytoma , Korner et al 2004, Kitlinska et al 2005, Cleary et al 2007), but no systematic survey of the expression of these genes has been performed so far in benign and malignant tumors. Thus, we measured by qPCR the mRNA levels of NPY and its five receptors in these tumors.…”

Section: Discussionmentioning

confidence: 99%

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Expression of trophic amidated peptides and their receptors in benign and malignant pheochromocytomas: high expression of adrenomedullin RDC1 receptor and implication in tumoral cell survival

Thouënnon¹,

Aimar²,

Tanguy³

et al. 2010

Endocrine-Related Cancer

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Pheochromocytomas are catecholamine-producing tumors which are generally benign, but which can also present as or develop into malignancy. Molecular pathways of malignant transformation remain poorly understood. Pheochromocytomas express various trophic peptides which may influence tumoral cell behavior. Here, we investigated the expression of trophic amidated peptides, including pituitary adenylate cyclase-activating polypeptide (PACAP), neuropeptide Y (NPY), and adrenomedullin (AM), and their receptors in benign and malignant pheochromocytomas in order to assess their potential role in chromaffin cell tumorigenesis and malignant transformation. PACAP, NPY, and AM are expressed in the majority of pheochromocytomas studied; NPY exhibiting the highest mRNA levels relative to reference genes. Although median gene expression or peptide levels were systematically lower in malignant compared to benign tumors, no statistically significant difference was found. Among all the receptors of these peptides that were analyzed, only the AM receptor RDC1 displayed a differential expression between benign and malignant pheochromocytomas. This receptor exhibited a fourfold higher expression in malignant than in benign tumors. AM and stromal cell-derived factor 1, which has also been described as a ligand for RDC1, increased the number of human pheochromocytoma cells in primary culture and exerted anti-apoptotic activity on rat pheochromocytoma PC12 cells. In addition, RDC1 gene silencing decreased the number of viable PC12 cells. This study shows the expression of several trophic peptides and their receptors in benign and malignant pheochromocytomas, and suggests that AM and its RDC1 receptor could be involved in chromaffin cell tumorigenesis through pro-survival effects. Therefore, AM and RDC1 may represent valuable targets for the treatment of malignant pheochromocytomas.

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Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 99%

Expression of trophic amidated peptides and their receptors in benign and malignant pheochromocytomas: high expression of adrenomedullin RDC1 receptor and implication in tumoral cell survival

Thouënnon¹,

Aimar²,

Tanguy³

et al. 2010

Endocrine-Related Cancer

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“…NPY is one of the most important adipocyte regulatory factors [13][14][15][16]. Several articles had provided evidence that NPY is produced in subcutaneous and visceral adipose tissue [17,18].…”

Section: Discussionmentioning

confidence: 99%

“…We performed Real time reverse transcription-PCR using the ICycler iQ Detection System (Bio-Rad). We amplified cDNA for 40 cycles using the TaqMan PCR Reagent Kit and pre-designed primers and fluorescein-labeled probes from Applied Biosystems for human NPY1R, NPY2R and NPY5R, as described [15], according to the manufacturer's procedure.…”

Section: Reverse Transcription-pcrmentioning

confidence: 99%

Neuropeptide Y promotes adipogenic differentiation in primary cultured human adipose-derived stem cells

Liu

Fang

et al. 2018

Endocr J

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Abstract. Neuropeptide Y (NPY) is an important neurotransmitter in the control of energy metabolism. Several studies have shown that obesity is associated with increased levels of NPY in the hypothalamus. We hypothesized that the release of NPY has coordinated and integrated effects on energy metabolism in different tissues, such as adipocyte tissue, resulting in increased energy storage and decreased energy expenditure. Whether NPY has role in the molecular mechanism of human adipocyte tissue remains unclear. We established the model of human adipose derived stem cells (hADSCs) from human adipose tissue and differentiated it into adipocytes in the presence of NPY at different concentrations (10 -15 -10 -6 mmol/L). We then assessed hADSCs proliferation and differentiation by quantifying lipid accumulation and examining the expression levels of related adipocyte markers after differentiation. Furthermore, the specific markers of white adipocyte tissue (WAT) in hADSCs were also analyzed. The results showed that low doses of NPY stimulated hADSCs proliferation (p < 0.05), while high doses of NPY inhibited hADSCs proliferation (p < 0.05). NPY significantly promoted lipid accumulation and increased the size of lipid droplets during human adipogenic differentiation; the levels of adipocyte markers PPAR-γ and C/EBPα were also increased. At the same time, NPY also increased the levels of WAT markers Cidec and RIP140 after adipocyte differentiation. The results suggested high dose NPY inhibits the proliferation of hADSCs while promotes adipocyte differentiation and increases the expression of WAT markers. This may be the reason why increased levels of NPY can lead to a rise in body weight.Key words: Neuropeptide Y, Human adipose-derived stem cells, Adipocyte differentiation, White adipose tissue NEUROPEPTIDE Y (NPY) is a 36-amino acid neuropeptide, which is widely expressed in the central and peripheral nervous system. In the brain, NPY is found in many brain areas [1], including the hypothalamus, dentate gyrus, lateral thalamus and striatum, with the highest concentrations in the arcuate nucleus of the hypothalamus (Arc). NPY is implicated in the regulation of many physiological processes, including food intake and body energy balance. NPY also regulates cardiovascular, gastrointestinal, reproductive, endocrine and behavioural function [2][3][4]. Recently, studies have revealed that administration of NPY has profound metabolic effects throughout the body. One characteristic of obesity is the This overproduction of fat is associated with increased lipogenesis in different organs, such as liver and white adipose tissue (WAT). Several studies found that obesity is associated with elevated levels of NPY in the hypothalamus [5][6][7][8][9]. Adipose tissue is important for regulation of energy metabolism. A disturbance of metabolic processes, such as thermogenesis, lipogenesis and fatty acid oxidation, may contribute to the pathology of obesity. In order to increase our understanding of how NPY could be involved in the adipoc...

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“…These high NPY levels correlate with MYCN amplification and poor clinical outcome (Dötsch et al 1998). NPY induces NB tumour growth and angiogenesis (Kitlinska et al 2005). NY2R is the most common NPY receptor expressed in NB cells and blocking the binding of NPY to NY2R has been proposed as an approach to inhibit NB growth (Lu et al 2010).…”

Section: S Verissimo Et Al: Novel Neuroblastoma Targetsmentioning

confidence: 99%

Neuroblastoma therapy: what is in the pipeline?

Veríssimo¹,

Molenaar²,

Fitzsimons³

et al. 2011

Endocrine-Related Cancer

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Despite the expansion of knowledge about neuroblastoma (NB) in recent years, the therapeutic outcome for children with a high-risk NB has not significantly improved. Therefore, more effective therapies are needed. This might be achieved by aiming future efforts at recently proposed but not yet developed targets for NB therapy. In this review, we discuss the recently proposed molecular targets that are in clinical trials and, in particular, those that are not yet explored in the clinic. We focus on the selection of these molecular targets for which promising in vitro and in vivo results have been obtained by silencing/inhibiting them. In addition, these selected targets are involved at least in one of the NB tumorigenic processes: proliferation, anti-apoptosis, angiogenesis and/or metastasis. In particular, we will review a recently proposed target, the microtubule-associated protein (MAP) encoded by doublecortin-like kinase gene (DCLK1). DCLK1-derived MAPs are crucial for proliferation and survival of neuroblasts and are highly expressed not only in NB but also in other tumours such as gliomas. Additionally, we will discuss neuropeptide Y, its Y2 receptor and cathepsin L as examples of targets to decrease angiogenesis and metastasis of NB. Furthermore, we will review the micro-RNAs that have been proposed as therapeutic targets for NB. Detailed investigation of these not yet developed targets as well as exploration of multi-target approaches might be the key to a more effective NB therapy, i.e. increasing specificity, reducing toxicity and avoiding long-term side effects.

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Differential Effects of Neuropeptide Y on the Growth and Vascularization of Neural Crest–Derived Tumors

Cited by 127 publications

References 40 publications

Expression of trophic amidated peptides and their receptors in benign and malignant pheochromocytomas: high expression of adrenomedullin RDC1 receptor and implication in tumoral cell survival

Expression of trophic amidated peptides and their receptors in benign and malignant pheochromocytomas: high expression of adrenomedullin RDC1 receptor and implication in tumoral cell survival

Neuropeptide Y promotes adipogenic differentiation in primary cultured human adipose-derived stem cells

Neuroblastoma therapy: what is in the pipeline?

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