Abstract
Glioblastoma multiforme (GBM) is an aggressive, Grade IV astrocytoma with a poor survival rate, primarily due to the GBM tumor cells migrating away from the primary tumor site along the nanotopography of white matter tracts and blood vessels. It is unclear whether this nanotopography influences the biomechanical properties (i.e. cytoskeletal stiffness) of GBM tumor cells. Although GBM tumor cells have an innate propensity to migrate, we believe this capability is enhanced due to the influence of nanotopography on the tumor cells’ biomechanical properties. In this study, we used an aligned nanofiber film that mimics the nanotopography in the tumor microenvironment to investigate the mechanical properties of GBM tumor cells in vitro. The data demonstrate that the cytoskeletal stiffness, cell traction stress, and focal adhesion area were significantly lower in the GBM tumor cells compared to healthy astrocytes. Moreover, the cytoskeletal stiffness was significantly reduced when cultured on aligned nanofiber films compared to smooth and randomly aligned nanofiber films. Gene expression analysis showed that tumor cells cultured on the aligned nanotopography upregulated key migratory genes and downregulated key proliferative genes. Therefore, our data suggest that the migratory potential is elevated when GBM tumor cells are migrating along aligned nanotopographical substrates.
Highlights
Glioblastoma multiforme (GBM) is an aggressive malignant brain tumor that accounts for 45.6% of primary brain tumors[1]
By examining the cytoskeletal stiffness, cytoskeletal organization, and gene expression of GBM cells cultured on aligned nanofibers, randomly aligned nanofibers, smooth film, and tissue culture polystyrene (TCPS), we identified substrate topography is correlative with the GBM tumor cells’ propensity to be in a more migratory or proliferative state
We investigated how the cytoskeletal mechanical properties of GBM tumor cells correlate to their migration potential
Summary
Glioblastoma multiforme (GBM) is an aggressive malignant brain tumor that accounts for 45.6% of primary brain tumors[1]. Cellular biomechanics are responsible for a variety of biological functions in eukaryotic cells, including migration, differentiation, morphogenesis, and proliferation[7,8] These processes are largely dependent on the cytoskeleton structure and its response to the surrounding extracellular matrix (ECM). The remodeling of the ECM and formation of the actin-rich membrane protrusions affect the cells’ deformation, altering their ability to stretch and contract, thereby abetting cellular invasion by allowing cells to migrate through tissues much faster than www.nature.com/scientificreports/. The tumor microenvironment, including nanotopography and substrate stiffness, has played a key role in the biomechanical, proliferative, and migratory properties of GBM cells[24,25,26,27,28,29,30,31]. In addition to modeling GBM migration[24,25,26,27,28,30], electrospun nanofibers have been used as a model for breast cancer cell invasion[34] and embryonic myogenesis[35]
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