Neuroendocrine Regulation of Neuroblastoma
Dai H. Chung
Department of Pediatric Surgery
Vanderbilt Children’s Hospital
2200 Children’s Way, Suite 4150
The Chung laboratory seeks a comprehensive understanding of the neuroendocrine regulation of neuroblastoma, the most common extra-cranial solid tumor in infants and children. In particular, Dr. Chung’s laboratory has had a long-standing interest in the role of gastrin-releasing peptide receptor (GRPR), a member of G-protein coupled receptor family, and its ligand in neuroblastoma cell growth, differentiation and metastasis. We have determined the relative importance of differential expression of GRPR in clinically aggressive undifferentiated neuroblastoma, and also have discerned the critical role of its ligand, gastrin-releasing peptide (GRP), as a significant autocrine growth factor for neuroblastoma. Our laboratory has also had a focus in delineating a crucial role of phosphatidylinositol 3-kinase (PI3K) pathway as the essential intracellular signal transduction mechanism responsible for GRPR-mediated tumorigenesis in neuroblastoma. We have recently identified that PI3K regulates MYNC, a key oncogene in neuroblastoma. Using various pharmacological and targeted silencing techniques, our recent work has demonstrated an important finding of PI3K-mediated activation of angiogenesis. Moreover, silencing of GRPR showed significant attenuation of neuroblastoma liver metastasis in our orthotopic xenograft model. Current investigations center on understanding the tumor host microenvironment in liver metastasis, the stromal regulation of differentiation and the role of sonic hedgehog signaling in the activation of PI3K pathway. Dr. Chung has recently joined Vanderbilt University Medical Center to establish the ‘Center of Excellence in Neuroblastoma Research’ in an effort to develop novel therapeutic interventions for translational applications. His laboratory will work closely with pediatric oncologists with basic science interests in neuroblastoma cell biology as well as in the development of translational clinical programs.