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Neuropeptide Y and its Y2 receptor: potential targets in neuroblastoma therapy.
Oncogene. 2010 Oct 14; 29(41):5630-42.O

Abstract

Neuroblastomas are pediatric tumors that develop from sympathetic precursors and express neuronal proteins, such as neuropeptide Y (NPY). NPY is a sympathetic neurotransmitter acting via multiple receptors (Y1-Y5R). Both NPY and Y2Rs are commonly expressed in neuroblastoma cell lines and tissues. The peptide secreted from neuroblastomas stimulates tumor cell proliferation and angiogenesis. As both processes are Y2R-mediated, the aim of this study was to assess Y2R as a potential therapeutic target for neuroblastoma. In vitro, Y2R antagonist (BIIE0246) prevented activation of p44/42 mitogen-activated protein kinase (MAPK) induced by endogenous NPY, which resulted in decreased proliferation and induction of Bim-mediated apoptosis. Similar growth-inhibitory effects were achieved with NPY small interfering RNA (siRNA) and Y2R siRNA. In vivo, Y2R antagonist significantly inhibited growth of SK-N-BE(2) and SK-N-AS xenografts, which was associated with decreased activation of p44/42 MAPK, as well as reduced proliferation (Ki67) and increased apoptosis (TdT-mediated dUTP nick end labeling; TUNEL). The Y2R antagonist also exerted an antiangiogenic effect. In vitro, it reduced the proliferation of endothelial cells induced by neuroblastoma-conditioned media. Consequently, the Y2R antagonist-treated xenografts had decreased vascularization and a high degree of focal fibrosis. In human neuroblastoma tissues, the expression of Y2R was observed in both tumor and endothelial cells, while NPY was predominantly expressed in neuroblastoma cells. In summary, Y2R is a promising new target for neuroblastoma therapy affecting both cancer cells and tumor vasculature.

Authors+Show Affiliations

Department of Physiology and Biophysics, Georgetown University, Washington, DC 20057, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

20676138

Citation

Lu, C, et al. "Neuropeptide Y and Its Y2 Receptor: Potential Targets in Neuroblastoma Therapy." Oncogene, vol. 29, no. 41, 2010, pp. 5630-42.
Lu C, Everhart L, Tilan J, et al. Neuropeptide Y and its Y2 receptor: potential targets in neuroblastoma therapy. Oncogene. 2010;29(41):5630-42.
Lu, C., Everhart, L., Tilan, J., Kuo, L., Sun, C. C., Munivenkatappa, R. B., Jönsson-Rylander, A. C., Sun, J., Kuan-Celarier, A., Li, L., Abe, K., Zukowska, Z., Toretsky, J. A., & Kitlinska, J. (2010). Neuropeptide Y and its Y2 receptor: potential targets in neuroblastoma therapy. Oncogene, 29(41), 5630-42. https://doi.org/10.1038/onc.2010.301
Lu C, et al. Neuropeptide Y and Its Y2 Receptor: Potential Targets in Neuroblastoma Therapy. Oncogene. 2010 Oct 14;29(41):5630-42. PubMed PMID: 20676138.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Neuropeptide Y and its Y2 receptor: potential targets in neuroblastoma therapy. AU - Lu,C, AU - Everhart,L, AU - Tilan,J, AU - Kuo,L, AU - Sun,C-C J, AU - Munivenkatappa,R B, AU - Jönsson-Rylander,A-C, AU - Sun,J, AU - Kuan-Celarier,A, AU - Li,L, AU - Abe,K, AU - Zukowska,Z, AU - Toretsky,J A, AU - Kitlinska,J, Y1 - 2010/08/02/ PY - 2010/8/3/entrez PY - 2010/8/3/pubmed PY - 2010/11/17/medline SP - 5630 EP - 42 JF - Oncogene JO - Oncogene VL - 29 IS - 41 N2 - Neuroblastomas are pediatric tumors that develop from sympathetic precursors and express neuronal proteins, such as neuropeptide Y (NPY). NPY is a sympathetic neurotransmitter acting via multiple receptors (Y1-Y5R). Both NPY and Y2Rs are commonly expressed in neuroblastoma cell lines and tissues. The peptide secreted from neuroblastomas stimulates tumor cell proliferation and angiogenesis. As both processes are Y2R-mediated, the aim of this study was to assess Y2R as a potential therapeutic target for neuroblastoma. In vitro, Y2R antagonist (BIIE0246) prevented activation of p44/42 mitogen-activated protein kinase (MAPK) induced by endogenous NPY, which resulted in decreased proliferation and induction of Bim-mediated apoptosis. Similar growth-inhibitory effects were achieved with NPY small interfering RNA (siRNA) and Y2R siRNA. In vivo, Y2R antagonist significantly inhibited growth of SK-N-BE(2) and SK-N-AS xenografts, which was associated with decreased activation of p44/42 MAPK, as well as reduced proliferation (Ki67) and increased apoptosis (TdT-mediated dUTP nick end labeling; TUNEL). The Y2R antagonist also exerted an antiangiogenic effect. In vitro, it reduced the proliferation of endothelial cells induced by neuroblastoma-conditioned media. Consequently, the Y2R antagonist-treated xenografts had decreased vascularization and a high degree of focal fibrosis. In human neuroblastoma tissues, the expression of Y2R was observed in both tumor and endothelial cells, while NPY was predominantly expressed in neuroblastoma cells. In summary, Y2R is a promising new target for neuroblastoma therapy affecting both cancer cells and tumor vasculature. SN - 1476-5594 UR - https://www.unboundmedicine.com/medline/citation/20676138/Neuropeptide_Y_and_its_Y2_receptor:_potential_targets_in_neuroblastoma_therapy_ L2 - http://dx.doi.org/10.1038/onc.2010.301 DB - PRIME DP - Unbound Medicine ER -