Glioblastoma Cells Use an Integrin- and CD44-Mediated Motor-Clutch Mode of Migration in Brain Tissue

• DOI: 10.1007/s12195-024-00799-x
• Publication Date: 2024-03-04T16:02:40Z
• Authors: Sarah M. Anderson; Marcus Kelly; David J. Odde
• Keywords: Original Article; Article

Abstract Purpose Glioblastoma (GBM) is an aggressive malignant brain tumor with 2 year survival rates of 6.7% (Stupp et al. in J Clin Oncol Off Am Soc 25:4127–4136, 2007; Mohammed Rep Pract Radiother 27:1026–1036, 2002). One key characteristic the disease ability glioblastoma cells to migrate rapidly and spread throughout healthy tissue (Lefranc 23:2411–2422, 2005; Hoelzinger Natl Cancer Inst 21:1583–1593, 2007). To develop treatments that effectively target cell migration, it important understand fundamental mechanism driving migration tissue. Several models have been proposed, including motor-clutch, bleb-based motility, osmotic engine models. Methods Here we utilized confocal imaging measure traction dynamics speeds mouse organotypic slices identify mode migration. Results We found nearly all cell-vasculature interactions reflected pulling, rather than pushing, on vasculature at leading edge, a finding consistent motor-clutch inconsistent model or confined Reducing myosin motor activity, component model, was decrease speed high doses for types U251 6 low-passage patient-derived xenograft lines (3 proneural 3 mesenchymal subtypes). Variable responses were low doses, which predicts biphasic relationship between motor-to-clutch ratio. Targeting molecular clutches integrins CD44 slowed cells. Conclusions Overall find most through ex vivo, both CD44, as well motors, play role constituting adhesive clutch.