The mechanical rigidity of the extracellular matrix regulates the structure, motility, and proliferation of glioma cells
By T. Ulrich, E. de Juan Pardo, Sanjay Kumar. Cancer Research, 2009
888 citations recorded by the source corpus.
Glioblastoma multiforme (GBM) is a malignant astrocytoma of the central nervous system associated with a median survival time of 15 months, even with aggressive therapy. This rapid progression is due in part to the diffuse infiltration of single tumor cells into the brain parenchyma, which is thought to involve aberrant interactions between tumor cells and the extracellular matrix (ECM). Here we test the hypothesis that mechanical cues from the ECM contribute to key tumor cell properties relevant to invasion. We cultured a series of glioma cell lines (U373-MG, U87-MG, U251-MG, SNB19, C6) on fibronectin-coated polymeric ECM substrates of defined mechanical rigidity and investigated the role of ECM rigidity in regulating tumor cell structure, migration, and proliferation. On highly rigid ECMs, tumor cells spread extensively, form prominent stress fibers and mature focal adhesions, and migrate rapidly. As ECM rigidity is lowered to values comparable to normal brain tissue, tumor cells appear rounded and fail to productively migrate. Remarkably, cell proliferation is also strongly regulated by ECM rigidity, with cells dividing much more rapidly on rigid than compliant ECMs. Pharmacological inhibition of nonmuscle myosin II-based contractility blunts this rigidity-sensitivity and rescues cell motility on highly compliant substrates. Collectively, our results provide support for a novel model in which ECM rigidity provides a transformative, microenvironmental cue that acts through actomyosin contractility to regulate the invasive properties of GBM tumor cells.
Subfields: Biomedical Engineering, Cell Biology
View Paper: https://www.semanticscholar.org/paper/72afcffc28ea7cffac4e968d927ba22e2b0bf4d3
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Citations in the corpus
- Force Fluctuations within Focal Adhesions Mediate ECM-Rigidity Sensing to Guide Directed Cell Migration (2012, background): “…to epithelial-to-mesenchymal transition (Guo et al., 2006; de Rooij et al., 2005), development of the nervous system (Flanagan et al., 2002; Koch et al., 2012), innate immunity (Mandeville et al., 1997), as well as cancer metastasis (Paszek et al., 2005; Wozniak et al., 2003; Ulrich et al., 2009).”
- Physical traits of cancer (2020, background): “Today, there are numerous studies showing how thematerial properties—in particular, the stiffness of themicroenvironment—are central to many traits of cancer (79), including proliferation (80, 81), angiogenesis (82), metabolism (83), invasion (84–86), andmigration andmetastasis (87–89) (Fig.”
- Matrix Stiffness Modulates Proliferation, Chemotherapeutic Response and Dormancy in Hepatocellular Carcinoma Cells (2011, background): “More recently increased matrix stiffness has been shown to promote cellular proliferation in glioma cells (23).”