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.

Details

Title
VEGF expression correlates with neuronal differentiation and predicts a favorable prognosis in patients with neuroblastoma
Author
Wen-Chin, Weng 1 ; Kuan-Hung, Lin 2 ; Pei-Yi, Wu 3 ; Ho, Ya-Hsuan 2 ; Yen-Lin, Liu 4   VIAFID ORCID Logo  ; Bo-Jeng, Wang 3 ; Chien-Chin, Chen 5 ; Yueh-Chien, Lin 2 ; Yung-Feng Liao 3 ; Wang-Tso, Lee 6 ; Wen-Ming Hsu 7 ; Lee, Hsinyu 8   VIAFID ORCID Logo 

1  Department of Pediatrics, National Taiwan University Hospital and National Taiwan University, College of Medicine, Taipei, Taiwan; Department of Life Science, National Taiwan University, Taipei, Taiwan 
2  Department of Life Science, National Taiwan University, Taipei, Taiwan 
3  Institute of Cellular and Organismic Biology, Academia Sinica, Taipei, Taiwan 
4  Department of Pediatrics, National Taiwan University Hospital and National Taiwan University, College of Medicine, Taipei, Taiwan; Department of Pediatrics, Taipei Medical University Hospital, Taipei, Taiwan 
5  Chia-Yi Christian Hospital, Chiayi, Taiwan; Department of Cosmetic Science, Chia Nan University of Pharmacy & Science, Chiayi, Taiwan 
6  Department of Pediatrics, National Taiwan University Hospital and National Taiwan University, College of Medicine, Taipei, Taiwan 
7  Department of Surgery, National Taiwan University Hospital and National Taiwan University, College of Medicine, Taipei, Taiwan 
8  Department of Life Science, National Taiwan University, Taipei, Taiwan; Department of Electrical Engineering, National Taiwan University, Taipei, Taiwan; Angiogenesis Research Center, National Taiwan University, Taipei, Taiwan; Research Center for Developmental Biology and Regenerative Medicine, National Taiwan University, Taipei, Taiwan; Center for Biotechnology, National Taiwan University, Taipei, Taiwan 
Pages
1-11
Publication year
2017
Publication date
Sep 2017
Publisher
Nature Publishing Group
e-ISSN
20452322
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41598-017-11637-8
ProQuest document ID
1953984131
Copyright
© 2017. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.