Hyaluronic acid induces ROCK-dependent amoeboid migration in glioblastoma cells
| Autor: | Yixiao Cui, Jose Otero, Joel Pepper, Sara L. Cole, Jessica O. Winter |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Adult
Gliding motility Cell Population Biomedical Engineering Motility Cell morphology Article Extracellular matrix 03 medical and health sciences 0302 clinical medicine Cell Movement Cell Line Tumor medicine Humans General Materials Science Hyaluronic Acid Amoeba education Actin 030304 developmental biology 0303 health sciences education.field_of_study Chemistry Mesenchymal stem cell Cell biology medicine.anatomical_structure 030220 oncology & carcinogenesis Glioblastoma |
| Zdroj: | Biomater Sci |
| ISSN: | 2047-4849 2047-4830 |
| DOI: | 10.1039/d0bm00505c |
| Popis: | Glioblastoma (GBM) is the most aggressive and deadly adult brain tumor, primarily because of its high infiltrative capacity and development of resistance to therapy. Although GBM cells are typically believed to migrate via mesenchymal (e.g., fibroblast-like) migration modes, amoeboid (e.g., leucocyte-like) migration modes have been identified and may constitute a salvage pathway. However, the mesenchymal to amoeboid transition (MAT) process in GB is not well characterized, most likely because most culture models induce MAT via pharmacological or genetic inhibition conditions that are far from physiological. In this study, we examined the ability of hyaluronic acid (HA) content in three-dimensional collagen (Col) hydrogels to induce MAT in U87 GBM cells. HA and Col are naturally-occurring components of the brain extracellular matrix (ECM). In pure Col gels, U87 cells displayed primarily mesenchymal behaviors, including elongated cell morphology, clustered actin and integrin expression, and crawling migration behaviors. Whereas an increasing population of cells displaying amoeboid behaviors, including rounded morphology, cortical actin expression, low/no integrin expression, and squeezing or gliding motility, were observed with increasing HA content (0.1-0.2 wt% in Col). Consistent with amoeboid migration, these behaviors were abrogated by ROCK inhibition with the non-specific small molecule inhibitor Y27632. Toward identification of histological MAT classification criteria, we also examined the correlation between cell and nuclear aspect ratio (AR) in Col and Col-HA gels, finding that nuclear AR has a small variance and is not correlated to cell AR in HA-rich gels. These results suggest that HA may regulate GBM cell motility in a ROCK-dependent manner. |
| Databáze: | OpenAIRE |
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