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

TJ Grundy1,2, E De Leon1, KR Griffin1, BW Stringer3, BW Day3, B Fabry4, J Cooper-White5 and GM O'Neill1,2

  1. Kids Research Institute, The Children's Hospital at Westmead, 2145 NSW Australia
  2. Discipline of Child and Adolescent Health, University of Sydney, NSW Australia
  3. Brain Cancer Research Unit, QIMR Berghofer Medical Research Institute, 4006 QLD Australia
  4. Department of Physics, University of Erlangen-Nuremberg, Germany
  5. Tissue Engineering and Microfluidics Laboratory, AIBN, QLD Australian

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.