P-14 Aryl Hydrocarbon Receptor Suppresses Tumor Progression of Neuroblastoma
by 陳輔卿, 2015-09-14 19:35, 人氣(726)

Aryl Hydrocarbon Receptor Suppresses Tumor Progression of Neuroblastoma


                             Pei-Yi Wu1, Yung-Feng Liao1, Wen-Ming Hsu2 and Hsinyu Lee3

1Institute of Cellular and Organismic Biology, Academia Sinica, Taipei, Taiwan

2Department of Surgery, National Taiwan University Hospital and National Taiwan  
 College of Medicine, Taipei, Taiwan

3Department of Life Science, National Taiwan University, Taipei, Taiwan




Neuroblastoma (NB) is the most common malignant disease of infancy. MYCN amplification is a prognostic factor for NB and is a sign of highly malignant disease and poor patient prognosis. However, how MYCN expression is regulated in NB remains unclear. In our previous study, aryl hydrocarbon receptor (AHR) was found to be inversely correlated to MYCN expression in NB. Positive AHR immunostaining correlated to the differentiated histology of NB and predicted better prognosis outcome of patients. By using NB cell lines as an in nitro model, we found overexpression of AHR downregulated MYCN expression and promoted cell differentiation. The evidence suggested AHR indeed is an important factor that affects NB cell behavior. However, the role of AHR in regulating NB tumor progression still needs further investigation.


AHR inducible expression cell line (stNB-V1-AI) was established and employed in in vivo mice xenograft model. In addition, NB therapy experiments by using AHR endogenous ligand, Kynurenine (Kyn), were examined in vitro and in vivo.


Doxycycline treatment in the daily drinking water significantly suppressed the tumor growth of stNB-V1-AI cells inoculated nude mice. Kyn promoted cell differentiation and adhesion in SK-N-SH cells. In vivo, Kyn significantly prolong the survival of TH-MYCN transgenic mice and suppress metastasis of NB in the xenograft model. By metastasis PCR array, the tumor metastasis suppressor gene Kiss-1 was suggested to be involved in the Kyn suppressed NB cell metastasis pathway. Kyn treatments significantly upregulated the gene expression level of Kiss-1. The induction of cell adhesion by Kyn was also efficiently blocked by Kiss-1 antagonist (Kiss-234).


Our results suggested that AHR overexpression or activation could suppress tumor progression of NB. The endogenous ligand of AHR, Kyn, has the great therapeutic potential for the future NB treatment.