An overview of neuroblastoma cell lineage phenotypes andin vitromodels

Abstract

This review was conducted to present the main neuroblastoma (NB) clinical characteristics and the most common genetic alterations present in these pediatric tumors, highlighting their impact in tumor cell aggressiveness behavior, including metastatic development and treatment resistance, and patients’ prognosis. The distinct three NB cell lineage phenotypes, S-type, N-type, and I-type, which are characterized by unique cell surface markers and gene expression patterns, are also reviewed. Finally, an overview of the most used NB cell lines currently available for in vitro studies and their unique cellular and molecular characteristics, which should be taken into account for the selection of the most appropriate model for NB pre-clinical studies, is presented. These valuable models can be complemented by the generation of NB reprogrammed tumor cells or organoids, derived directly from patients’ tumor specimens, in the direction toward personalized medicine. Impact statement This review provides an update on the mostly used cell line in vitro models for neuroblastoma (NB), a heterogeneous disease with high metastatic potential and resistance to treatment. The genetic and phenotypic profiles of the most used NB cell lines in the last 10 years are presented, considering the molecular markers that are involved in the distinct NB tumor phenotypes, including distinct core regulatory circuitries and non-coding RNAs. This gathered information can assist in the selection of the most appropriate NB in vitro model, based on the specific goals and objectives of each study.

Integrative transcriptomic and proteomic meta-analysis of Zika viral infection reveals potential mechanisms for oncolytic therapy in neuroblastoma

“…The cell viability of 10/15 neuroblastoma cell lines is significantly reduced to below 20% following ZIKV infection and these observations are apparent despite the differences in the cell line, ZIKV strain, viral MOI and the type of assay performed (Table 1). SK-N-Be(1) and SK-N-Be(2) cells are from bone marrow metastasis from the same patient before and after treatment, respectively, and are both highly susceptible to ZIKV. Thus, Table 1 identifies that ZIKV can target neuroblastoma cells which originate from the primary tumour, metastatic sites and metastatic sites which are resistant to standard neuroblastoma therapy.…”

“…Determining the interactions and mechanisms underpinning this may yield opportunities to develop a paediatric neuroblastoma therapy based on ZIKV NS4B. ZIKV NS4B has 130 known host interaction partners in SK-N-BE(2) neuroblastoma cells (14). Here, we analyse this interactome and identify multiple pathways which we, and others, have implicated during ZIKV infection of neuroblastoma cells: including mitochondrial-, lipid metabolism- and ER-associated processes (Figure 6).…”

“…The ZIKV NS4B interactome in SK-N-BE(2) paediatric neuroblastoma cells were sourced from IMEx (IM-26452) and mapped in Cytoscape (3.9.1). 130 host NS4B interaction partners were submitted to STRING for high confidence (0.7) evidence-based physical subnetwork analysis, followed by integration with the NS4B interactome to identify the interaction of NS4B with host protein complexes.…”

“…Additional data incorporated into the Cytoscape map includes known ZIKV dependency factors and the interaction of ZIKV NS2B-3 with the Mammalian Translocon. ZIKV dependency factors were sourced for paediatric SK-N-BE(2) neuroblastoma (14), GSC (15), hiPSC-NPC (16), HEK293FT (15) and HeLa cells (17).…”

In Vitro Modeling of the Blood–Brain Barrier for the Study of Physiological Conditions and Alzheimer’s Disease

“…Similarly, the use of neuroblastoma cells may be a good choice when studying the cholinergic hypothesis of AD. As undifferentiated cells, they depict the immature cholinergic neuronal cells; however, as tumor cells, the toleration for oxidative stress and high glycolysis may lead to incorrect results in experiments [ 128 ].…”