Single-cell tracking reveals super-spreading cells with high persistence in invasive brain cancer

Nousi, Aimilia; Søgaard, Maria Tangen; Jauffred, Liselotte

doi:10.1101/2020.10.06.327676

Cited by 4 publications

(2 citation statements)

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“…Strong cell-matrix interactions could explain invasion of GBM cells into Matrigel we found in this work. Mechanical properties of ECM may also play a role in GBM invasiveness, but have been found to have a limited role in cell migration away from the spheroid ( Nousi et al, 2020 ). Interestingly, when we embedded dissociated cortical cells in Matrigel, invasiveness of GBM cells increased.…”

Section: Discussionmentioning

confidence: 99%

3D models of glioblastoma interaction with cortical cells

Abedin

Michelhaugh²,

Mittal³

et al. 2023

Front. Bioeng. Biotechnol.

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Introduction: Glioblastoma (GBM) invasiveness and ability to infiltrate deep into the brain tissue is a major reason for the poor patient prognosis for this type of brain cancer. Behavior of glioblastoma cells, including their motility, and expression of invasion-promoting genes such as matrix metalloprotease-2 (MMP2), are strongly influenced by normal cells found in the brain parenchyma. Cells such as neurons may also be influenced by the tumor, as many glioblastoma patients develop epilepsy. In vitro models of glioblastoma invasiveness are used to supplement animal models in a search for better treatments, and need to combine capability for high-throughput experiments with capturing bidirectional interactions between GBM and brain cells.Methods: In this work, two 3D in vitro models of GBM-cortical interactions were investigated. A matrix-free model was created by co-culturing GBM and cortical spheroids, and a matrix-based model was created by embedding cortical cells and a GBM spheroid in Matrigel.Results: Rapid GBM invasion occurred in the matrix-based model, and was enhanced by the presence of cortical cells. Little invasion occurred in the matrix-free model. In both types of models, presence of GBM cells resulted in a significant increase in paroxysmal neuronal activity.Discussion: Matrix-based model may be better suited for studying GBM invasion in an environment that includes cortical cells, while matrix-free model may be useful in investigation of tumor-associated epilepsy.

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Section: Discussionmentioning

confidence: 99%

3D models of glioblastoma interaction with cortical cells

Abedin

Michelhaugh²,

Mittal³

et al. 2023

Front. Bioeng. Biotechnol.

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show abstract

“…Following the criteria discussed in ref. 27 , we terminated tracks when cells had migrated either i) along the edge of the image for more than 15 min, ii) less than 50 μm over their entire trajectory to remove the contribution from immobile/dead cells, as well as when cells either iii) divided or iv) merged. The quality and reliability of cell motility analysis is highly dependent on the image acquisition procedures.…”

Section: Methodsmentioning

confidence: 99%

Tumor spheroids accelerate persistently invading cancer cells

Audoin

Søgaard

Jauffred

2022

Preprint

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Glioblastoma brain tumors form in brains’ white matter and remains one of the most lethal cancers despite intensive therapy and surgery. The complex morphology of these tumors includes infiltrative growth and gain of cell motility. Therefore, various brain-mimetic model systems have been developed to investigate invasion dynamics. Despite this, exactly how gradients of cell density, chemical signals and metabolites influence individual cells’ migratory behavior remains elusive. Here we show that the gradient field – induced by the spheroid – accelerates cells’ invasion of the extracellular matrix. We show that cells are pushed away from the spheroid along a radial gradient, as predicted by a biased persistent random walk (BPRW). Thus, our results grasp in a simple model the complex behavior of metastasizing cells. We anticipate that this well-defined and quantitative assay could be instrumental in the development of new anti-cancer strategies.

show abstract

Tumor spheroids accelerate persistently invading cancer cells

Audoin

Søgaard²,

Jauffred³

2022

Sci Rep

Self Cite

View full text Add to dashboard Cite

Glioblastoma brain tumors form in the brain’s white matter and remain one of the most lethal cancers despite intensive therapy and surgery. The complex morphology of these tumors includes infiltrative growth and gain of cell motility. Therefore, various brain-mimetic model systems have been developed to investigate invasion dynamics. Despite this, exactly how gradients of cell density, chemical signals and metabolites influence individual cells’ migratory behavior remains elusive. Here we show that the gradient field induced by the spheroid—accelerates cells’ invasion of the extracellular matrix. We show that cells are pushed away from the spheroid along a radial gradient, as predicted by a biased persistent random walk. Thus, our results grasp in a simple model the complex behavior of metastasizing cells. We anticipate that this well-defined and quantitative assay could be instrumental in the development of new anti-cancer strategies.

show abstract

Single-cell tracking reveals super-spreading cells with high persistence in invasive brain cancer

Cited by 4 publications

References 100 publications

3D models of glioblastoma interaction with cortical cells

3D models of glioblastoma interaction with cortical cells

Tumor spheroids accelerate persistently invading cancer cells

Tumor spheroids accelerate persistently invading cancer cells

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