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Updated: Apr 20, 2026
Differentiation of the SH-SY5Y Human Neuroblastoma Cell Line
Published on: February 17, 2016
Proteomics of dedifferentiation of SK-N-BE2 neuroblastoma cells
Ravi Kanth Rao Saini1, Sanaz Attarha2, Claire da Silva Santos3
1Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden; Sahlgrenska Cancer Center, University of Gothenburg, Gothenburg, Sweden.
Abstract:
Neuroblastoma develops through processes which include cellular dedifferentiation. Ability of tumors to form spheroids is one of the manifestations of dedifferentiation and carcinogenic transformation. To study mechanisms of dedifferentiation of neuroblastoma cells, we generated spheroids and performed a proteomics study to compare the spheroids with parental SK-N-BE2 cells. We observed that dedifferentiation induced extensive changes in the proteome profiles of the cells, which affected more than 30% of detected cellular proteins. Using mass spectrometry, we identified 239 proteins affected by dedifferentiation into spheroids as compared to the parental cells. These proteins represented such regulatory processes as transcription, cell cycle regulation, apoptosis, cell adhesion, metabolism, intracellular transport, stress response, and angiogenesis. A number of potent regulators of stemness, differentiation and cancer were detected as subnetworks formed by the identified proteins. Our validation tissue microarray study of 30 neuroblastoma cases confirmed that two of the identified proteins, DISC1 and DNA-PKcs, had their expression increased in advanced malignancies. Thus, our report unveiled extensive changes of the cellular proteome upon dedifferentiation of neuroblastoma cells, indicated top subnetworks and clusters of molecular mechanisms involved in dedifferentiation, and provided candidate biomarkers for clinical studies.
Insights
Neuroblastoma dedifferentiation involves significant proteome changes. Key proteins like DISC1 and DNA-PKcs increase in advanced tumors, offering potential biomarkers for neuroblastoma progression.
Area of Science:
- Molecular Biology
- Oncology
- Proteomics
Background:
- Neuroblastoma, a pediatric cancer, arises from cellular dedifferentiation.
- Tumor spheroid formation is a hallmark of neuroblastoma dedifferentiation and malignant transformation.
Purpose of the Study:
- To investigate the proteomic changes associated with neuroblastoma cell dedifferentiation.
- To identify molecular mechanisms and potential biomarkers involved in neuroblastoma dedifferentiation.
Main Methods:
- Generation of neuroblastoma spheroids from parental SK-N-BE2 cells.
- Proteomic analysis using mass spectrometry to compare spheroid and parental cell proteomes.
- Validation of candidate protein expression in 30 neuroblastoma tissue samples via tissue microarray.
Main Results:
- Dedifferentiation induced significant proteome alterations, affecting over 30% of cellular proteins.
- Identified 239 proteins involved in key regulatory processes including transcription, cell cycle, apoptosis, and metabolism.
- DISC1 and DNA-PKcs expression was elevated in advanced neuroblastoma malignancies.
Conclusions:
- Neuroblastoma dedifferentiation triggers widespread proteomic remodeling.
- Identified protein subnetworks highlight critical mechanisms in dedifferentiation and cancer progression.
- DISC1 and DNA-PKcs represent promising candidate biomarkers for clinical evaluation in neuroblastoma.
