Glioma cell migration in confined microchannels via a motor-clutch mechanism

Prahl, L.; Stanslaski, Maria R.; Vargas, Pablo Agustín; Piel, Matthieu; Odde, David J.

doi:10.1101/500843

Cited by 3 publications

(2 citation statements)

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“…Indeed, similarly designed microchannels have been used to study the effect of different drugs or chemoattractant on migration rate of various cancer cells 55 . Microchannel system was also applied to isolate brain tumour stem cells (BTSC) 56 , and to study the mechanical properties of migrating GBM cells under confinement 57 . However, to the best of our knowledge of published literature in the public domain it has never been applied to study the effect of NP treatment on GBM migration ability.…”

Section: Discussionmentioning

confidence: 99%

Transferrin-targeted porous silicon nanoparticles reduce glioblastoma cell migration across tight extracellular space

Sheykhzadeh

Luo

Peng

et al. 2020

Sci Rep

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Mortality of glioblastoma multiforme (GBM) has not improved over the last two decades despite medical breakthroughs in the treatment of other types of cancers. Nanoparticles hold tremendous promise to overcome the pharmacokinetic challenges and off-target adverse effects. However, an inhibitory effect of nanoparticles by themselves on metastasis has not been explored. In this study, we developed transferrin-conjugated porous silicon nanoparticles (Tf@pSiNP) and studied their effect on inhibiting GBM migration by means of a microfluidic-based migration chip. This platform, designed to mimic the tight extracellular migration tracts in brain parenchyma, allowed high-content time-resolved imaging of cell migration. Tf@pSiNP were colloidally stable, biocompatible, and their uptake into GBM cells was enhanced by receptor-mediated internalisation. The migration of Tf@ pSiNP-exposed cells across the confined microchannels was suppressed, but unconfined migration was unaffected. The pSiNP-induced destabilisation of focal adhesions at the leading front may partially explain the migration inhibition. More corroborating evidence suggests that pSiNP uptake reduced the plasticity of GBM cells in reducing cell volume, an effect that proved crucial in facilitating migration across the tight confined tracts. We believe that the inhibitory effect of Tf@pSiNP on cell migration, together with the drug-delivery capability of pSiNP, could potentially offer a disruptive strategy to treat GBM.Glioblastoma multiforme (GBM) is the most prevalent and biologically aggressive type of primary brain tumour in adults 1 . Standard treatment is maximal surgical resection of a tumour followed by radiotherapy and temozolomide as an adjuvant chemotherapy 2 . Despite these advanced treatments, the survival rate of GBM patients is still less than 5% over five years, with a median overall survival of merely 15-23 months 3 . The factors that contribute to the high mortality are multifactorial. First and foremost, the diffuse invasion of GBM into brain parenchyma precludes complete surgical resection which leads to high recurrence 4 . Recurring GBM are usually multi-drug resistant, rendering chemotherapy ineffective 5 . On rare occasions, the high invasion and migration potential even leads to extracranial metastases 6 .The mechanisms of GBM invasion and migration are complex and encompasses the regulation of tumour microenvironment and of the molecular arrangement within the migrating GBM cells 7 . To enable migration across the small perivascular space, GBM cells have been shown to reduce their volume by releasing cytoplasmic fluid 8 . The reduction in cell size is particularly instrumental to GBM invasion into healthy brain tissue, since www.nature.com/scientificreports www.nature.com/scientificreports/ recombinant human Fibroblast Growth Factor basic (Gibco, PHG0024), and StemPro Neural Supplement (Gibco, A10508-01). The culture media also contained GlutaMAX (Gibco, 35050-061) and penicillin/streptomycin (Gibco, 15140-122). Cells were only used betwe...

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Section: Discussionmentioning

confidence: 99%

Transferrin-targeted porous silicon nanoparticles reduce glioblastoma cell migration across tight extracellular space

Sheykhzadeh

Luo

Peng

et al. 2020

Sci Rep

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“…Literature surrounding the in vitro activity of LAT A in glioma cell lines, also supports the findings of this study. A study from Prahl et al (2018), found that LAT A treatment decreased cell migration, decreasing further with an increased LAT A concentration. The study from Ketchen (2019), carried out a two-dimensional assay studying the migration distances of a range of inhibitors.…”

Section: Latrunculin a Displays The Greatest Effect On Decreasing Cel...mentioning

confidence: 99%

High resolution analysis of anti-migratory inhibitors in high grade glioma treatment

Burns

2022

Fields: Journal of Huddersfield Student Research

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IntroductionGlioblastoma Multiforme (GBM) is an extremely aggressive form of glioma tumour. The characteristically invasive properties of GBM contribute to the poor prognosis in suffers. This study focuses on the therapeutic potential of four anti-migratory drugs - 6-bromo- indirubin-3’oxime (BIO), CCG-1423, Latrunculin A (LAT A) and Lithium Chloride (LiCl), in vitro. The migration distances of migrating GBM cells and cell circularity for each treatment and an untreated control were measured and statistically analysed.MethodsGBM spheroids of the U251 cell line were treated with BIO, CCG-1423, LAT A or LiCl plus an untreated control in preparation for this study. These were sectioned using immunohistochemical techniques and scanned prior to the study using QuPath. Cell migration was measured from the perimeter of the tumour spheroid to the edge of the migrating cell. Cell circularity was obtained using the ‘cell circularity index’ function. The cell circularity of the migrating cells was obtained separately to the cell circularity of the cells within the spheroid. This repeated for each section for each spheroid for each study. The data obtained was analysed in SPSS.ResultsEach of the treatments showed significant statistical differences compared the control spheroid for the migration distance measurements. LAT A was shown to have the greatest effect in decreasing the migration distances. The analysis of the cell circularity indicated that the migrated cells were significantly more rounded than the tumour cells for each treatment. The ‘cell circularity index’ indicated the migrated cells were more rounded than those within the tumour spheroid across each of the treatments.ConclusionThe cell migration distance study suggests further study, to analyse the effects of these drugs in vivo, as they each demonstrated anti-migratory effects on the GBM cells. The ‘cell circularity index’ study should be amended to more accurately represent the changes in morphology during GBM cell migration.

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