Establishment and biological characterization of a panel of glioblastoma multiforme (GBM) and GBM variant oncosphere cell lines

Zev A. Binder, Kelli M. Wilson, Vafi Salmasi, Brent A. Orr, Charles G. Eberhart, I. Mei Siu, Michael Lim, Jon D. Weingart, Alfredo Quinones-Hinojosa, Chetan Bettegowda, Amin B. Kassam, Alessandro Olivi, Henry Brem, Gregory J. Riggins, Gary L. Gallia

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Objective: Human tumor cell lines form the basis of the majority of present day laboratory cancer research. These models are vital to studying the molecular biology of tumors and preclinical testing of new therapies. When compared to traditional adherent cell lines, suspension cell lines recapitulate the genetic profiles and histologic features of glioblastoma multiforme (GBM) with higher fidelity. Using a modified neural stem cell culture technique, here we report the characterization of GBM cell lines including GBM variants. Methods: Tumor tissue samples were obtained intra-operatively and cultured in neural stem cell conditions containing growth factors. Tumor lines were characterized in vitro using differentiation assays followed by immunostaining for lineage-specific markers. In vivo tumor formation was assayed by orthotopic injection in nude mice. Genetic uniqueness was confirmed via short tandem repeat (STR) DNA profiling. Results: Thirteen oncosphere lines derived from GBM and GBM variants, including a GBM with PNET features and a GBM with oligodendroglioma component, were established. All unique lines showed distinct genetic profiles by STR profiling. The lines assayed demonstrated a range of in vitro growth rates. Multipotency was confirmed using in vitro differentiation. Tumor formation demonstrated histologic features consistent with high grade gliomas, including invasion, necrosis, abnormal vascularization, and high mitotic rate. Xenografts derived from the GBM variants maintained histopathological features of the primary tumors. Conclusions: We have generated and characterized GBM suspension lines derived from patients with GBMs and GBM variants. These oncosphere cell lines will expand the resources available for preclinical study.

Original languageEnglish (US)
Article numbere0150271
JournalPLoS One
Volume11
Issue number3
DOIs
StatePublished - Mar 1 2016
Externally publishedYes

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oncospheres
Glioblastoma
Tumors
Cells
cell lines
Cell Line
neoplasms
Neoplasms
Stem cells
Microsatellite Repeats
stem cells
Suspensions
Neural Stem Cells
microsatellite repeats
Molecular biology
DNA fingerprinting
Cell culture
Heterografts
molecular biology
growth factors

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Binder, Z. A., Wilson, K. M., Salmasi, V., Orr, B. A., Eberhart, C. G., Siu, I. M., ... Gallia, G. L. (2016). Establishment and biological characterization of a panel of glioblastoma multiforme (GBM) and GBM variant oncosphere cell lines. PLoS One, 11(3), [e0150271]. https://doi.org/10.1371/journal.pone.0150271

Establishment and biological characterization of a panel of glioblastoma multiforme (GBM) and GBM variant oncosphere cell lines. / Binder, Zev A.; Wilson, Kelli M.; Salmasi, Vafi; Orr, Brent A.; Eberhart, Charles G.; Siu, I. Mei; Lim, Michael; Weingart, Jon D.; Quinones-Hinojosa, Alfredo; Bettegowda, Chetan; Kassam, Amin B.; Olivi, Alessandro; Brem, Henry; Riggins, Gregory J.; Gallia, Gary L.

In: PLoS One, Vol. 11, No. 3, e0150271, 01.03.2016.

Research output: Contribution to journalArticle

Binder, ZA, Wilson, KM, Salmasi, V, Orr, BA, Eberhart, CG, Siu, IM, Lim, M, Weingart, JD, Quinones-Hinojosa, A, Bettegowda, C, Kassam, AB, Olivi, A, Brem, H, Riggins, GJ & Gallia, GL 2016, 'Establishment and biological characterization of a panel of glioblastoma multiforme (GBM) and GBM variant oncosphere cell lines', PLoS One, vol. 11, no. 3, e0150271. https://doi.org/10.1371/journal.pone.0150271
Binder, Zev A. ; Wilson, Kelli M. ; Salmasi, Vafi ; Orr, Brent A. ; Eberhart, Charles G. ; Siu, I. Mei ; Lim, Michael ; Weingart, Jon D. ; Quinones-Hinojosa, Alfredo ; Bettegowda, Chetan ; Kassam, Amin B. ; Olivi, Alessandro ; Brem, Henry ; Riggins, Gregory J. ; Gallia, Gary L. / Establishment and biological characterization of a panel of glioblastoma multiforme (GBM) and GBM variant oncosphere cell lines. In: PLoS One. 2016 ; Vol. 11, No. 3.
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AU - Orr, Brent A.

AU - Eberhart, Charles G.

AU - Siu, I. Mei

AU - Lim, Michael

AU - Weingart, Jon D.

AU - Quinones-Hinojosa, Alfredo

AU - Bettegowda, Chetan

AU - Kassam, Amin B.

AU - Olivi, Alessandro

AU - Brem, Henry

AU - Riggins, Gregory J.

AU - Gallia, Gary L.

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N2 - Objective: Human tumor cell lines form the basis of the majority of present day laboratory cancer research. These models are vital to studying the molecular biology of tumors and preclinical testing of new therapies. When compared to traditional adherent cell lines, suspension cell lines recapitulate the genetic profiles and histologic features of glioblastoma multiforme (GBM) with higher fidelity. Using a modified neural stem cell culture technique, here we report the characterization of GBM cell lines including GBM variants. Methods: Tumor tissue samples were obtained intra-operatively and cultured in neural stem cell conditions containing growth factors. Tumor lines were characterized in vitro using differentiation assays followed by immunostaining for lineage-specific markers. In vivo tumor formation was assayed by orthotopic injection in nude mice. Genetic uniqueness was confirmed via short tandem repeat (STR) DNA profiling. Results: Thirteen oncosphere lines derived from GBM and GBM variants, including a GBM with PNET features and a GBM with oligodendroglioma component, were established. All unique lines showed distinct genetic profiles by STR profiling. The lines assayed demonstrated a range of in vitro growth rates. Multipotency was confirmed using in vitro differentiation. Tumor formation demonstrated histologic features consistent with high grade gliomas, including invasion, necrosis, abnormal vascularization, and high mitotic rate. Xenografts derived from the GBM variants maintained histopathological features of the primary tumors. Conclusions: We have generated and characterized GBM suspension lines derived from patients with GBMs and GBM variants. These oncosphere cell lines will expand the resources available for preclinical study.

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