Back to Search
Start Over
Activation of Aryl Hydrocarbon Receptor by Kynurenine Impairs Progression and Metastasis of Neuroblastoma
- Source :
- Cancer Research. 79:5550-5562
- Publication Year :
- 2019
- Publisher :
- American Association for Cancer Research (AACR), 2019.
-
Abstract
- Neuroblastoma is the most common malignant disease of infancy, and amplification of the MYCN oncogene is closely associated with poor prognosis. Recently, expression of MYCN was shown to be inversely correlated with aryl hydrocarbon receptor (AHR) expression in neuroblastoma, and overexpression of AHR downregulated MYCN expression, promoting cell differentiation. Therefore, we further investigated the potential of AHR to serve as a prognostic indicator or a therapeutic target in neuroblastoma. First, the clinical significance of AHR in neuroblastoma was examined. Positive AHR immunostaining strongly correlated with differentiated histology of neuroblastoma and predicted better survival for patients. The mouse xenograft model showed that overexpression of AHR significantly suppressed neuroblastoma tumor growth. In addition, activation of AHR by the endogenous ligand kynurenine inhibited cell proliferation and promoted cell differentiation in vitro and in vivo. kynurenine treatment also upregulated the expression of KISS1, a tumor metastasis suppressor, and attenuated metastasis in the xenograft model. Finally, analysis of KISS1 levels in neuroblastoma patient tumors using the R2: Genomics Analysis and Visualization Platform revealed that KISS1 expression positively correlated with AHR, and high KISS1 expression predicted better survival for patients. In conclusion, our results indicate that AHR is a novel prognostic biomarker for neuroblastoma, and that overexpression or activation of AHR offers a new therapeutic possibility for patients with neuroblastoma. Significance: These findings show that AHR may function as a tumor suppressor in childhood neuroblastoma, potentially influencing the aetiologic and therapeutic targeting of the disease.
- Subjects :
- Male
0301 basic medicine
Cancer Research
Cellular differentiation
Metastasis
Mice
Neuroblastoma
chemistry.chemical_compound
0302 clinical medicine
Cell Movement
Basic Helix-Loop-Helix Transcription Factors
Medicine
Genes, Tumor Suppressor
Child
Kynurenine
Kisspeptins
Mice, Inbred BALB C
N-Myc Proto-Oncogene Protein
biology
Cell Differentiation
respiratory system
Gene Expression Regulation, Neoplastic
Oncology
Child, Preschool
030220 oncology & carcinogenesis
Disease Progression
Female
Childhood Neuroblastoma
Mice, Nude
03 medical and health sciences
Cell Line, Tumor
Animals
Humans
Metastasis suppressor
neoplasms
Cell Proliferation
business.industry
Cell growth
Gene Amplification
Infant, Newborn
Infant
Aryl hydrocarbon receptor
medicine.disease
respiratory tract diseases
030104 developmental biology
Receptors, Aryl Hydrocarbon
chemistry
biology.protein
Cancer research
business
Subjects
Details
- ISSN :
- 15387445 and 00085472
- Volume :
- 79
- Database :
- OpenAIRE
- Journal :
- Cancer Research
- Accession number :
- edsair.doi.dedup.....dad571dc0a0aaecaf55767702b4ebff0
- Full Text :
- https://doi.org/10.1158/0008-5472.can-18-3272