PUBLICATION
Neuroblastoma differentiation in vivo excludes cranial tumors
- Authors
- Treffy, R.W., Rajan, S.G., Jiang, X., Nacke, L.M., Malkana, U.A., Naiche, L.A., Bergey, D.E., Santana, D., Rajagopalan, V., Kitajewski, J.K., O'Bryan, J.P., Saxena, A.
- ID
- ZDB-PUB-211006-11
- Date
- 2021
- Source
- Developmental Cell 56(19): 2752-2764.e6 (Journal)
- Registered Authors
- Saxena, Ankur
- Keywords
- differentiating microenvironment, live imaging, neuroblastoma, neuronal differentiation, pediatric cancer
- MeSH Terms
-
- Animals
- Brain-Derived Neurotrophic Factor/metabolism
- Cell Differentiation/physiology*
- Cell Line, Tumor
- Cell Movement/physiology
- Female
- Humans
- Male
- Mice
- Neural Crest/metabolism
- Neuroblastoma/metabolism*
- Neurons/cytology
- Neurons/physiology
- Signal Transduction
- Transplantation, Heterologous/methods
- Tretinoin/metabolism
- Tretinoin/pharmacology
- Tumor Microenvironment
- Zebrafish/metabolism
- PubMed
- 34610330 Full text @ Dev. Cell
Citation
Treffy, R.W., Rajan, S.G., Jiang, X., Nacke, L.M., Malkana, U.A., Naiche, L.A., Bergey, D.E., Santana, D., Rajagopalan, V., Kitajewski, J.K., O'Bryan, J.P., Saxena, A. (2021) Neuroblastoma differentiation in vivo excludes cranial tumors. Developmental Cell. 56(19):2752-2764.e6.
Abstract
Neuroblastoma (NB), the most common cancer in the first year of life, presents almost exclusively in the trunk. To understand why an early-onset cancer would have such a specific localization, we xenotransplanted human NB cells into discrete neural crest (NC) streams in zebrafish embryos. Here, we demonstrate that human NB cells remain in an undifferentiated, tumorigenic state when comigrating posteriorly with NC cells but, upon comigration into the head, differentiate into neurons and exhibit decreased survival. Furthermore, we demonstrate that this in vivo differentiation requires retinoic acid and brain-derived neurotrophic factor signaling from the microenvironment, as well as cell-autonomous intersectin-1-dependent phosphoinositide 3-kinase-mediated signaling, likely via Akt kinase activation. Our findings suggest a microenvironment-driven explanation for NB's trunk-biased localization and highlight the potential for induced differentiation to promote NB resolution in vivo.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping