A key reason for malignant glioma recurrence after radical tumor resection is the failure to control individual invading tumor cells that have moved away from the primary tumor mass. The purpose of this study was to assess the role of ROCK (Rho-kinase), a signaling protein in the Rho GTPase pathway, in malignant glioma invasion in a three-dimensional model system. Primary glioblastoma (GBM) explants or multicellular spheroids were implanted into a three-dimensional collagen type I matrix. Individual tumor cells detached from the explants or spheroids and invaded the matrix, or invaded human fetal astrocyte spheroids. Treatment of implanted spheroids or explants with selective pharmacological inhibitors of ROCK was found to significantly decrease invasion. Inhibition of ROCK did not affect glioma cell or human astrocyte survival or proliferation. The identification of the Rho/ROCK pathway as being important for glioma cell invasion might be of therapeutic value in treating highly invasive glioblastoma.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.81339 |
| Date | January 2004 |
| Creators | Hering, Ramm |
| Publisher | McGill University |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Format | application/pdf |
| Coverage | Master of Science (Division of Neuroscience.) |
| Rights | All items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated. |
| Relation | alephsysno: 002166335, proquestno: AAIMR06402, Theses scanned by UMI/ProQuest. |
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