Matrix Proteins Induce Neuroblastoma Cell Differentiation without Altering Cell Growth

Kidowaki, Takuro; Thiele, Carol J.; Kleinman, Hynda K.; Israel, Mark A.

doi:10.1159/000163670

Cited by 7 publications

(3 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These molecular components act in concert to sense and process signals from the ECM [9-12] and to mediate cell shape and cytoarchitecture. In addition, altering the biochemical composition of the ECM itself induces morphological differentiation of neuroblastoma cells [13-15]. Together, these data strongly hint that signals encoded in the ECM may play a significant role in guiding NB differentiation.…”

Section: Resultsmentioning

confidence: 99%

Extracellular matrix rigidity modulates neuroblastoma cell differentiation and N-myc expression

et al. 2010

View full text Add to dashboard Cite

Neuroblastoma is a pediatric malignancy characterized by tremendous clinical heterogeneity, in which some tumors are extremely aggressive while others spontaneously differentiate into benign forms. Because the degree of differentiation correlates with prognosis, and because differentiating agents such as retinoic acid (RA) have proven to decrease mortality, much effort has been devoted to identifying critical regulators of neuroblastoma differentiation in the cellular microenvironment, including cues encoded in the extracellular matrix (ECM). While signaling between tumor cells and the ECM is classically regarded to be based purely on biochemical recognition of ECM ligands by specific cellular receptors, a number of recent studies have made it increasingly clear that the biophysical properties of the ECM may also play an important role in this cross-talk. Given that RA-mediated neuroblastoma differentiation is accompanied by profound changes in cell morphology and neurite extension, both of which presumably rely upon mechanotransductive signaling systems, it occurred to us that mechanical cues from the ECM might also influence RA-mediated differentiation, which in turn might regulate clinically-relevant aspects of neuroblastoma biology. In this study, we tested this hypothesis by subjecting a series of neuroblastoma culture models to ECM microenvironments of varying mechanical stiffness and examined the regulatory role of ECM stiffness in proliferation, differentiation, and expression of tumor markers. We find that increasing ECM stiffness enhances neuritogenesis and suppresses cell proliferation. Remarkably, increasing ECM stiffness also reduces expression of N-Myc, a transcription factor involved in multiple aspects of oncogenic proliferation that is used for evaluating prognosis and clinical grading of neuroblastoma. Furthermore, the addition of RA enhances all of these effects for all ECM stiffnesses tested. Together, our data strongly support the notion that the mechanical signals from the cellular microenvironment influence neuroblastoma differentiation and do so synergistically with RA. These observations support further investigation of the role of microenvironmental mechanical signals in neuroblastoma proliferation and differentiation and suggest that pharmacological agents that modulate the underlying mechanotransductive signaling pathways may have a role in neuroblastoma therapy.

show abstract

Section: Resultsmentioning

confidence: 99%

Extracellular matrix rigidity modulates neuroblastoma cell differentiation and N-myc expression

et al. 2010

View full text Add to dashboard Cite

show abstract

“…The rigidity or stiffness of ECM also affects the cellular behavior of NB cells including stem cell differentiation, neurite extension, proliferation, and malignant potential of these cells [47][48][49]. Several studies have shown that alterations in the biochemical composition of ECM promote morphological differentiation of NB cells [50][51][52]. Lam et al have shown that rigidity of ECM increases neuroblastoma cell differentiation and N-Myc expression [53].…”

Section: Targeting the Extracellular Matrixmentioning

confidence: 99%

Targeting the Tumor Microenvironment in Neuroblastoma: Recent Advances and Future Directions

Joshi

2020

Cancers

View full text Add to dashboard Cite

Neuroblastoma (NB) is the most common pediatric tumor malignancy that originates from the neural crest and accounts for more than 15% of all the childhood deaths from cancer. The neuroblastoma cancer research has long been focused on the role of MYCN oncogene amplification and the contribution of other genetic alterations in the progression of this malignancy. However, it is now widely accepted that, not only tumor cells, but the components of tumor microenvironment (TME), including extracellular matrix, stromal cells and immune cells, also contribute to tumor progression in neuroblastoma. The complexity of different components of tumor stroma and their resemblance with surrounding normal tissues pose huge challenges for therapies targeting tumor microenvironment in NB. Hence, the detailed understanding of the composition of the TME of NB is crucial to improve existing and future potential immunotherapeutic approaches against this childhood cancer. In this review article, I will discuss different components of the TME of NB and the recent advances in the strategies, which are used to target the tumor microenvironment in neuroblastoma.

show abstract

“…In the case of neuroblastoma cells, the crosstalk between cells and the ECM influences the differentiation outcome . In particular, differences in the ECM biochemical composition as well as in its rigidity induce morphological differences in neuroblastoma cells and in their differentiation process . The SH‐SY5Y cell line is a well‐described cell model for normal and pathological morpho‐functional neuronal mechanisms and processes: For this reason, it is of great interest in biological and biomedical sciences with translational clinical impacts on human health (e.g., in vitro cell model of dopaminergic neurons in Parkinson's disease, muscle and neurodegenerative diseases, and brain disorders)…”

Section: Introductionmentioning

confidence: 99%

Micro‐Raman detection of the differentiation state of SH‐SY5Y cells grown on silicon and aluminium substrates

Ricci

Sagini

Caponi

et al. 2018

J Raman Spectroscopy

View full text Add to dashboard Cite

SH‐SY5Y cell line is a model for neural diseases originating from neuroblastoma, a paediatric embryonal malignancy that may differentiate and regress to a benign state. By monitoring the differentiation in single living cells, it could be possible to reach a better understanding of the process and, consequently, to develop new therapeutic approaches. In this work, we investigated the potential of Raman microspectroscopy to monitor biochemical changes in single living SH‐SY5Y cells treated with a combination of retinoic acid (RA) and brain‐derived neurotrophic factor to stimulate the differentiation toward a neuronal phenotype. The results show that the spectroscopic analysis is able to detect biochemical alterations consistent with the differentiation process. Moreover, we investigated also the influence of the cell culture substrate on the treatment outcome. Silicon and aluminium are 2 materials suitable for the spectroscopic analysis and of interest in neuroscience applications. Even though silicon has an ensured biocompatibility, it is subject to alterations after the treatment with RA. Aluminium revealed to be a cost‐effective cell culture substrate for the RA and brain‐derived neurotrophic factor treatment of SH‐SY5Y cells and particularly suitable for Raman microspectroscopy.

show abstract

Matrix Proteins Induce Neuroblastoma Cell Differentiation without Altering Cell Growth

Cited by 7 publications

References 22 publications

Extracellular matrix rigidity modulates neuroblastoma cell differentiation and N-myc expression

Extracellular matrix rigidity modulates neuroblastoma cell differentiation and N-myc expression

Targeting the Tumor Microenvironment in Neuroblastoma: Recent Advances and Future Directions

Micro‐Raman detection of the differentiation state of SH‐SY5Y cells grown on silicon and aluminium substrates

Contact Info

Product

Resources

About