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ROCK Inhibition Facilitates In Vitro Expansion of Glioblastoma Stem-Like Cells

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dc.contributor.authorTilson, Samantha G.
dc.contributor.authorHaley, Elizabeth M.
dc.contributor.authorTriantafillu, Ursula L.
dc.contributor.authorDozier, David A.
dc.contributor.authorLangford, Catherine P.
dc.contributor.authorGillespie, G. Yancey
dc.contributor.authorKim, Yonghyun
dc.contributor.otherUniversity of Alabama Tuscaloosa
dc.contributor.otherUniversity of Alabama Birmingham
dc.date.accessioned2023-09-28T19:11:29Z
dc.date.available2023-09-28T19:11:29Z
dc.date.issued2015
dc.description.abstractDue to their stem-like characteristics and their resistance to existing chemo-and radiation therapies, there is a growing appreciation that cancer stem cells (CSCs) are the root cause behind cancer metastasis and recurrence. However, these cells represent a small subpopulation of cancer cells and are difficult to propagate in vitro. Glioblastoma is an extremely deadly form of brain cancer that is hypothesized to have a subpopulation of CSCs called glioblastoma stem cells (GSCs; also called brain tumor initiating cells, BTICs). We propose the use of selective Rho-kinase (ROCK) inhibitors, Y-27632 and fasudil, to promote GSC/BTIC-like cell survival and propagation in vitro. ROCK inhibitors have been implicated in suppressing apoptosis, and it was hypothesized that they would increase the number of GSC/BTIC-like cells grown in vitro and improve cloning efficiencies. Indeed, our data demonstrate that transient and continuous supplementation of non-toxic concentrations of Y-27632 and fasudil inhibited apoptosis, enhanced the cells' ability to form spheres, and increased stem cell marker expressing GSC/BTIC-like cell subpopulation. Our data indicated that pharmacological and genetic (siRNA) inhibitions of the ROCK pathway facilitates in vitro expansion of GSC/BTIC-like cells. Thus, ROCK pathway inhibition shows promise for future optimization of CSC culture media.en_US
dc.format.mediumelectronic
dc.format.mimetypeapplication/pdf
dc.identifier.citationTilson, S. G., Haley, E. M., Triantafillu, U. L., Dozier, D. A., Langford, C. P., Gillespie, G. Y., & Kim, Y. (2015). ROCK Inhibition Facilitates In Vitro Expansion of Glioblastoma Stem-Like Cells. In A. B. Hjelmeland (Ed.), PLOS ONE (Vol. 10, Issue 7, p. e0132823). Public Library of Science (PLoS). https://doi.org/10.1371/journal.pone.0132823
dc.identifier.doi10.1371/journal.pone.0132823
dc.identifier.orcidhttps://orcid.org/0000-0001-6344-1258
dc.identifier.orcidhttps://orcid.org/0000-0001-6436-9542
dc.identifier.orcidhttps://orcid.org/0000-0001-6318-5784
dc.identifier.urihttps://ir.ua.edu/handle/123456789/10993
dc.languageEnglish
dc.language.isoen_US
dc.publisherPLOS
dc.rights.licenseAttribution 4.0 International (CC BY 4.0)
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectRHO/ROCK PATHWAY
dc.subjectSELF-RENEWAL
dc.subjectMODELS
dc.subjectMAINTENANCE
dc.subjectAPOPTOSIS
dc.subjectSURVIVAL
dc.subjectTUMORS
dc.subjectLINES
dc.subjectMultidisciplinary Sciences
dc.titleROCK Inhibition Facilitates In Vitro Expansion of Glioblastoma Stem-Like Cellsen_US
dc.typeArticle
dc.typetext

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