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Understanding the Biological Basis of Glioblastoma Patient-derived Spheroids
K. Turnovcova, D. Marekova, T. Sursal, M. Krupova, R. Gandhi, P. Krupa, R. Kaiser, V. Herynek, D. Netuka, P. Jendelova, M. Jhanwar-Uniyal
Language English Country Greece
Document type Journal Article
NLK
Free Medical Journals
from 2004 to 2 years ago
Open Access Digital Library
from 2004-01-01
- MeSH
- AC133 Antigen analysis MeSH
- Spheroids, Cellular physiology MeSH
- Glioblastoma blood supply pathology MeSH
- Humans MeSH
- Mice MeSH
- Cell Line, Tumor MeSH
- Neoplastic Stem Cells physiology MeSH
- Brain Neoplasms blood supply pathology MeSH
- Neovascularization, Pathologic etiology MeSH
- Cell Movement MeSH
- Cell Proliferation MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Male MeSH
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
BACKGROUND/AIM: Resistance to glioblastoma (GB) therapy is attributed to the presence of glioblastoma stem cells (GSC). Here, we defined the behavior of GSC as it pertains to proliferation, migration, and angiogenesis. MATERIALS AND METHODS: Human-derived GSC were isolated and cultured from GB patient tumors. Xenograft GSC were extracted from the xenograft tumors, and spheroids were created and compared with human GSC spheroids by flow cytometry, migration, proliferation, and angiogenesis assays. Oct3/4 and Sox2, GFAP, and Ku80 expression was assessed by immunoanalysis. RESULTS: The xenograft model showed the formation of two different tumors with distinct characteristics. Tumors formed at 2 weeks were less aggressive with well-defined margins, whereas tumors formed in 5 months were diffuse and aggressive. Expression of Oct3/4 and Sox2 was positive in both human and xenograft GSC. Positive Ku80 expression in xenograft GSC confirmed their human origin. Human and xenograft GSC migrated vigorously in collagen and Matrigel, respectively. Xenograft GSC displayed a higher rate of migration and invasion than human GSC. CONCLUSION: Human GSC were more aggressive in growth and proliferation than xenograft GSC, while xenograft GSC had increased invasion and migration compared to human GSC. A simple in vitro spheroid system for GSC provides a superior platform for the development of precision medicine in the treatment of GB.
2nd Faculty of Medicine Charles University Prague Czech Republic
Department of Neurosurgery New York Medical College Westchester Medical Center Valhalla NY U S A
References provided by Crossref.org
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