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  Spatial heterogeneity of cell-matrix adhesive forces predicts human glioblastoma migration

Rezk, R., Jia, B. Z., Wendler, A., Dimov, I., Watts, C., Markaki, A. E., et al. (2020). Spatial heterogeneity of cell-matrix adhesive forces predicts human glioblastoma migration. Neuro-Oncology Advances, 2(1), vdaa081. doi:10.1093/noajnl/vdaa081.

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 Creators:
Rezk, Rasha1, Author
Jia, Bill Zong1, Author
Wendler, Astrid1, Author
Dimov, Ivan1, Author
Watts, Colin1, Author
Markaki, Athina E.1, Author
Franze, Kristian2, 3, Author           
Kabla, Alexandre J.1, Author
Affiliations:
1external, ou_persistent22              
2Abteilung Franze, Max-Planck-Zentrum für Physik und Medizin, Max Planck Institute for the Science of Light, Max Planck Society, ou_3596665              
3Friedrich-Alexander-Universität Erlangen-Nürnberg, External Organizations, DE, ou_3487833              

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Free keywords: cell migration, cell-matrix adhesion, glioblastoma
 Abstract: BACKGROUND: Glioblastoma (GBM) is a highly aggressive incurable brain tumor. The main cause of mortality in GBM patients is the invasive rim of cells migrating away from the main tumor mass and invading healthy parts of the brain. Although the motion is driven by forces, our current understanding of the physical factors involved in glioma infiltration remains limited. This study aims to investigate the adhesion properties within and between patients' tumors on a cellular level and test whether these properties correlate with cell migration.
METHODS: Six tissue samples were taken from spatially separated sections during 5-aminolevulinic acid (5-ALA) fluorescence-guided surgery. Navigated biopsy samples were collected from strongly fluorescent tumor cores, a weak fluorescent tumor rim, and nonfluorescent tumor margins. A microfluidics device was built to induce controlled shear forces to detach cells from monolayer cultures. Cells were cultured on low modulus polydimethylsiloxane representative of the stiffness of brain tissue. Cell migration and morphology were then obtained using time-lapse microscopy.
RESULTS: GBM cell populations from different tumor fractions of the same patient exhibited different migratory and adhesive behaviors. These differences were associated with sampling location and amount of 5-ALA fluorescence. Cells derived from weak- and nonfluorescent tumor tissue were smaller, adhered less well, and migrated quicker than cells derived from strongly fluorescent tumor mass.
CONCLUSIONS: GBM tumors are biomechanically heterogeneous. Selecting multiple populations and broad location sampling are therefore important to consider for drug testing.

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Language(s): eng - English
 Dates: 2020-07-03
 Publication Status: Issued
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 Identifiers: DOI: 10.1093/noajnl/vdaa081
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Title: Neuro-Oncology Advances
Source Genre: Journal
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Pages: - Volume / Issue: 2 (1) Sequence Number: - Start / End Page: vdaa081 Identifier: ISSN: 2632-2498