title: Differential response of patient-derived primary glioblastoma cells to environmental stiffness.
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.
authors.affiliation: Children's Cancer Research Unit, Kids Research Institute, The Children's Hospital at Westmead, Westmead, 2145, New South Wales, Australia.|Discipline of Paediatrics and Child Health, The University of Sydney, Sydney, 2000, New South Wales, Australia.
authors.forename: Thomas James
authors.initials: TJ
authors.lastname: Grundy
authors.affiliation: Children's Cancer Research Unit, Kids Research Institute, The Children's Hospital at Westmead, Westmead, 2145, New South Wales, Australia.
authors.forename: Ellen
authors.initials: E
authors.lastname: De Leon
authors.affiliation: Children's Cancer Research Unit, Kids Research Institute, The Children's Hospital at Westmead, Westmead, 2145, New South Wales, Australia.
authors.forename: Kaitlyn Rose
authors.initials: KR
authors.lastname: Griffin
authors.affiliation: Brain Cancer Research Unit &Leukaemia Foundation Research Unit, QIMR Berghofer Medical Research Institute, Brisbane, 4006, Queensland, Australia.
authors.forename: Brett William
authors.initials: BW
authors.lastname: Stringer
authors.affiliation: Brain Cancer Research Unit &Leukaemia Foundation Research Unit, QIMR Berghofer Medical Research Institute, Brisbane, 4006, Queensland, Australia.
authors.forename: Bryan William
authors.initials: BW
authors.lastname: Day
authors.affiliation: Department of Physics, University of Erlangen-Nuremberg, Germany.
authors.forename: Ben
authors.initials: B
authors.lastname: Fabry
authors.affiliation: Tissue Engineering and Microfluidics Laboratory, Australian Institute for Bioengineering and Nanotechnology, University of Queensland, St. Lucia, Queensland, Australia.
authors.forename: Justin
authors.initials: J
authors.lastname: Cooper-White
authors.affiliation: Children's Cancer Research Unit, Kids Research Institute, The Children's Hospital at Westmead, Westmead, 2145, New South Wales, Australia.|Discipline of Paediatrics and Child Health, The University of Sydney, Sydney, 2000, New South Wales, Australia.
authors.forename: Geraldine Margaret
authors.initials: GM
authors.lastname: O'Neill
mesh_terms: D008841:Actin Cytoskeleton / Q000502:physiology; D001932:Brain Neoplasms / Q000473:pathology* / Q000503:physiopathology*; D045744:Cell Line, Tumor; D002465:Cell Movement; D005909:Glioblastoma / Q000473:pathology* / Q000503:physiopathology*; D006801:Humans; D009361:Neoplasm Invasiveness; D018874:Spheroids, Cellular; D013499:Surface Properties