Induced differentiation inhibits sphere formation in neuroblastoma. Biochem Biophys Res Commun 2016 Aug 19;477(2):255-9
Date
06/15/2016Pubmed ID
27297102Pubmed Central ID
PMC5333757DOI
10.1016/j.bbrc.2016.06.053Scopus ID
2-s2.0-84976623361 (requires institutional sign-in at Scopus site) 14 CitationsAbstract
Neuroblastoma arises from the neural crest, the precursor cells of the sympathoadrenal axis, and differentiation status is a key prognostic factor used for clinical risk group stratification and treatment strategies. Neuroblastoma tumor-initiating cells have been successfully isolated from patient tumor samples and bone marrow using sphere culture, which is well established to promote growth of neural crest stem cells. However, accurate quantification of sphere-forming frequency of commonly used neuroblastoma cell lines has not been reported. Here, we show that MYCN-amplified neuroblastoma cell lines form spheres more frequently than non-MYCN-amplified cell lines. We also show that sphere formation is directly sensitive to cellular differentiation status. 13-cis-retinoic acid is a clinically used differentiating agent that induces a neuronal phenotype in neuroblastoma cells. Induced differentiation nearly completely blocked sphere formation. Furthermore, sphere formation was specifically FGF-responsive and did not respond to increasing doses of EGF. Taken together, these data suggest that sphere formation is an accurate method of quantifying the stemness phenotype in neuroblastoma.
Author List
Craig BT, Rellinger EJ, Alvarez AL, Dusek HL, Qiao J, Chung DHAuthor
Brian T. Craig MD Assistant Professor in the Surgery department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Batch Cell Culture TechniquesCell Differentiation
Cell Line, Tumor
Cellular Reprogramming
Humans
Neoplastic Stem Cells
Neuroblastoma
Spheroids, Cellular
