Differential response of patient-derived primary glioblastoma cells to environmental stiffness

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Grundy, Thomas James
De Leon, Ellen
Griffin, Kaitlyn Rose
Stringer, Brett William
Day, Bryan William
Fabry, Ben
Cooper-White, Justin
O'Neill, Geraldine Margaret
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2016
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Abstract

The ability of cancer cells to sense external mechanical forces has emerged as a significant factor in the promotion of cancer invasion. Currently there are conflicting reports in the literature with regard to whether glioblastoma (GBM) brain cancer cell migration and invasion is rigidity-sensitive. In order to address this question we have compared the rigidity-response of primary patient-derived GBM lines. Cells were plated on polyacrylamide gels of defined rigidity that reflect the diversity of the brain tissue mechanical environment, and cell morphology and migration were analysed by time-lapse microscopy. Invasiveness was assessed in multicellular spheroids embedded in 3D matrigel cultures. Our data reveal a range of rigidity-dependent responses between the patient-derived cell lines, from reduced migration on the most compliant tissue stiffness to those that are insensitive to substrate rigidity and are equally migratory irrespective of the underlying substrate stiffness. Notably, the rigidity-insensitive GBM cells show the greatest invasive capacity in soft 3D matrigel cultures. Collectively our data confirm both rigidity-dependent and independent behaviour in primary GBM patient-derived cells.

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Scientific Reports

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6

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© The Authors 2016. This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/

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Oncology and carcinogenesis

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Multidisciplinary Sciences

Science & Technology - Other Topics

EXTRACELLULAR-MATRIX

INITIATING CELLS

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Grundy, TJ; De Leon, E; Griffin, KR; Stringer, BW; Day, BW; Fabry, B; Cooper-White, J; O'Neill, GM, Differential response of patient-derived primary glioblastoma cells to environmental stiffness, Scientific Reports, 2016, 6, pp. 23353

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