VEGF expression correlates with neuronal differentiation and predicts a favorable prognosis in patients with neuroblastoma

doi:10.1038/s41598-017-11637-8

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Title:	VEGF expression correlates with neuronal differentiation and predicts a favorable prognosis in patients with neuroblastoma
Authors:	Weng, Wen-Chin Lin, Kuan-Hung Wu, Pei-Yi Ho, Ya-Hsuan Liu, Yen-Lin Wang, Bo-Jeng Chen, Chien-Chin Lin, Yueh-Chien Liao, Yung-Feng Lee, Wang-Tso Hsu, Wen-Ming Lee, Hsinyu
Contributors:	Natl Taiwan Univ Hosp, Dept Pediat Natl Taiwan Univ, Coll Med Natl Taiwan Univ, Dept Life Sci Acad Sinica, Inst Cellular & Organism Biol Taipei Med Univ Hosp, Dept Pediat Chia Yi Christian Hosp Chia Nan Univ Pharm & Sci, Dept Cosmet Sci Natl Taiwan Univ Hosp, Dept Surg Natl Taiwan Univ, Dept Elect Engn Natl Taiwan Univ, Angiogenesis Res Ctr Natl Taiwan Univ, Res Ctr Dev Biol & Regenerat Med Natl Taiwan Univ, Ctr Biotechnol
Keywords:	Anti-Angiogenesis Gene-Expression Messenger-Rna Up-Regulation Calreticulin Tumor Cells Growth Amplification Receptors
Date:	2017-09-11
Issue Date:	2018-11-30 15:56:46 (UTC+8)
Publisher:	Nature Publishing Group
Abstract:	Neuroblastoma (NB) is a childhood cancer with a low survival rate and great metastatic potential. Vascular endothelial growth factor (VEGF), an angiogenesis factor, has been found to be involved in CRT-related neuronal differentiation of NB cells. In this study, we further confirmed the role VEGF in NB through mouse xenograft model and clinical analysis from NB patients. In xenograft experiments, CRT overexpression effectively inhibited the tumor growth. In addition, the mRNA and protein levels of VEGF and differentiation marker GAP-43 were upregulated by induced CRT expression. However, no significant correlation between the expression level of VEGF and microvessel density was observed in human NB tumors, suggesting a novel mechanism of VEGF participating in NB tumorigenesis through an angiogenesis-independent pathway. In NB patients' samples, mRNA expression levels of CRT and VEGF were positively correlated. Furthermore, positive VEGF expression by immunostaining of NB tumors was found to correlate well with histological grade of differentiation and predicted a favorable prognosis. In conclusion, our findings suggest that VEGF is a favorable prognostic factor of NB and might affect NB tumor behavior through CRT-driven neuronal differentiation rather than angiogenesis that might shed light on a novel therapeutic strategy to improve the outcome of NB.
Relation:	Scientific Reports, v.7, pp.11212
Appears in Collections:	[Dept. of Cosmetic Science and institute of cosmetic science] Periodical Articles

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