Ring cell migration assay identifies distinct effects of extracellular matrix proteins on cancer cell migration

Chen, Hui; Nalbantoglu, Joséphine

doi:10.1186/1756-0500-7-183

Cited by 16 publications

(13 citation statements)

References 23 publications

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“…This indicates a generic pro-migratory function of a protein interface adjacent to viscous polysaccharide. In previous work, glioma cell migration was primarily assessed in single-cell migration assays, using cell suspensions after enzymatic dispersion (Nakada et al 2013 ; Chen and Nalbantoglu 2014 ). However, when tested as tumor-like multicellular spheroids, which allow cells to establish cell–cell junctions, both U-251 and E-98 cells migrated collectively, as a cohesive sheet of cells, along the rBM-hyaluronan interface (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…In recent years, different assays were developed to model glioma microenvironments of the brain tissue and test the extent and mechanisms of glioma cell invasion (Rao et al 2014 ; Rape et al 2014 ). Widely used 2D assays are based on coating of the culture dish with ECM molecules, including laminin, fibronectin or collagen (Nakada et al 2013 ; Chen and Nalbantoglu 2014 ). However, these models lack crucial parameters of 3D brain environments which modulate migration mechanisms, including (1) low substrate stiffness, (2) anatomically complex 3D organization, (3) 3D space confinements which enable adhesion-dependent and adhesion-independent migration, and (4) molecularly rich ECM composition maintained by brain cells and containing chemotactic factors (Rape et al 2014 ).…”

Section: Introductionmentioning

confidence: 99%

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Recapitulating in vivo-like plasticity of glioma cell invasion along blood vessels and in astrocyte-rich stroma

Gritsenko

Leenders

Friedl

2017

Histochem Cell Biol

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Diffuse invasion of glioma cells into the brain parenchyma leads to nonresectable brain tumors and poor prognosis of glioma disease. In vivo, glioma cells can adopt a range of invasion strategies and routes, by moving as single cells, collective strands and multicellular networks along perivascular, perineuronal and interstitial guidance cues. Current in vitro assays to probe glioma cell invasion, however, are limited in recapitulating the modes and adaptability of glioma invasion observed in brain parenchyma, including collective behaviours. To mimic in vivo-like glioma cell invasion in vitro, we here applied three tissue-inspired 3D environments combining multicellular glioma spheroids and reconstituted microanatomic features of vascular and interstitial brain structures. Radial migration from multicellular glioma spheroids of human cell lines and patient-derived xenograft cells was monitored using (1) reconstituted basement membrane/hyaluronan interfaces representing the space along brain vessels; (2) 3D scaffolds generated by multi-layered mouse astrocytes to reflect brain interstitium; and (3) freshly isolated mouse brain slice culture ex vivo. The invasion patterns in vitro were validated using histological analysis of brain sections from glioblastoma patients and glioma xenografts infiltrating the mouse brain. Each 3D assay recapitulated distinct aspects of major glioma invasion patterns identified in mouse xenografts and patient brain samples, including individually migrating cells, collective strands extending along blood vessels, and multicellular networks of interconnected glioma cells infiltrating the neuropil. In conjunction, these organotypic assays enable a range of invasion modes used by glioma cells and will be applicable for mechanistic analysis and targeting of glioma cell dissemination.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Recapitulating in vivo-like plasticity of glioma cell invasion along blood vessels and in astrocyte-rich stroma

Gritsenko

Leenders

Friedl

2017

Histochem Cell Biol

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“…Metastasis is the leading cause of death for patients diagnosed with cancer. Tumor invasiveness is known to be enhanced by epithelial-mesenchymal transition (EMT), which confers metastatic properties upon cancer cells by increasing their migration [1,2]. Therefore, targeting tumor cell motility is an extremely important and meaningful challenge in the prevention of metastasis and improving the effectiveness of cancer treatment.…”

Section: Introductionmentioning

confidence: 99%

The Effect of 3′-Hydroxy-3,4,5,4′-Tetramethoxy -stilbene, the Metabolite of the Resveratrol Analogue DMU-212, on the Motility and Proliferation of Ovarian Cancer Cells

Nowicki

Skupin-Mrugalska

Józkowiak

et al. 2020

IJMS

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Targeting tumor cell motility and proliferation is an extremely important challenge in the prevention of metastasis and improving the effectiveness of cancer treatment. We recently published data revealing that DMU-214, the metabolite of firmly cytotoxic resveratrol analogue DMU-212, exerted significantly higher biological activity than the parent compound in ovarian cancer cells. The aim of the present study was to assess the molecular mechanism of the potential anti-migration and anti-proliferative effect of DMU-214 in ovarian cancer cell line SKOV-3. We showed that DMU-214 reduced the migratory capacity of SKOV-3 cells. The microarray analysis indicated ontology groups of genes involved in processes of negative regulation of cell motility and proliferation. Furthermore, we found DMU-214 triggered changes in expression of several migration- and proliferation-related genes (SMAD7, THBS1, IGFBP3, KLF4, Il6, ILA, SOX4, IL15, SRF, RGCC, GPR56) and proteins (GPR56, RGCC, SRF, SMAD7, THBS1), which have been shown to interact to each other to reduce cell proliferation and motility. Our study showed for the first time that DMU-214 displayed anti-migratory and anti-proliferative activity in SKOV-3 ovarian cancer cells. On the basis of whole transcriptome analysis of these cells, we provide new insight into the role of DMU-214 in inhibition of processes related to metastasis.

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“…Thus, while standard treatment strategies mainly focus on the bulk tumor mass, the deeper understanding of tumor cell invasion and the development of novel drugs for its inhibition is of major importance. Classical 2D cell culture or co-culture systems for tumor cell migration, like scratch assays, transwell/Boyden chamber assays or the coating of wells with extracellular matrix (ECM) components like collagen, fibronectin, or laminin [ 4 , 5 ] are rather simple and inexpensive. Yet, such standard methods do not allow for sufficiently assessing the invasive potential due to the absence of matrix components and barrier structures to be encountered by the invading cells.…”

Section: Introductionmentioning

confidence: 99%

Glioblastoma Tissue Slice Tandem-Cultures for Quantitative Evaluation of Inhibitory Effects on Invasion and Growth

Sidorcenco

Krahnen

Schulz

et al. 2020

Cancers

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Glioblastomas (GBMs) are the most malignant brain tumors and are essentially incurable even after extensive surgery, radiotherapy, and chemotherapy, mainly because of extensive infiltration of tumor cells into the adjacent normal tissue. Thus, the evaluation of novel drugs in malignant glioma treatment requires sophisticated ex vivo models that approach the authentic interplay between tumor and host environment while avoiding extensive in vivo studies in animals. This paper describes the standardized setup of an organotypic brain tissue slice tandem-culture system, comprising of normal brain tissue from adult mice and tumor tissue from human glioblastoma xenografts, and explore its utility for assessing inhibitory effects of test drugs. The microscopic analysis of vertical sections of the slice tandem-cultures allows for the simultaneous assessment of (i) the invasive potential of single cells or cell aggregates and (ii) the space occupying growth of the bulk tumor mass, both contributing to malignant tumor progression. The comparison of tissue slice co-cultures with spheroids vs. tissue slice tandem-cultures using tumor xenograft slices demonstrates advantages of the xenograft tandem approach. The direct and facile application of test drugs is shown to exert inhibitory effects on bulk tumor growth and/or tumor cell invasion, and allows their precise quantitation. In conclusion, we describe a straightforward ex vivo system mimicking the in vivo situation of the tumor mass and the normal brain in GBM patients. It reduces animal studies and allows for the direct and reproducible application of test drugs and the precise quantitation of their effects on the bulk tumor mass and on the tumor’s invasive properties.

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Ring cell migration assay identifies distinct effects of extracellular matrix proteins on cancer cell migration

Cited by 16 publications

References 23 publications

Recapitulating in vivo-like plasticity of glioma cell invasion along blood vessels and in astrocyte-rich stroma

Recapitulating in vivo-like plasticity of glioma cell invasion along blood vessels and in astrocyte-rich stroma

The Effect of 3′-Hydroxy-3,4,5,4′-Tetramethoxy -stilbene, the Metabolite of the Resveratrol Analogue DMU-212, on the Motility and Proliferation of Ovarian Cancer Cells

Glioblastoma Tissue Slice Tandem-Cultures for Quantitative Evaluation of Inhibitory Effects on Invasion and Growth

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