Dataset Information

The Human Glioblastoma Cell Culture Resource: Validated Cell Models Representing All Molecular Subtypes.

ABSTRACT: Glioblastoma (GBM) is the most frequent and malignant form of primary brain tumor. GBM is essentially incurable and its resistance to therapy is attributed to a subpopulation of cells called glioma stem cells (GSCs). To meet the present shortage of relevant GBM cell (GC) lines we developed a library of annotated and validated cell lines derived from surgical samples of GBM patients, maintained under conditions to preserve GSC characteristics. This collection, which we call the Human Glioblastoma Cell Culture (HGCC) resource, consists of a biobank of 48 GC lines and an associated database containing high-resolution molecular data. We demonstrate that the HGCC lines are tumorigenic, harbor genomic lesions characteristic of GBMs, and represent all four transcriptional subtypes. The HGCC panel provides an open resource for in vitro and in vivo modeling of a large part of GBM diversity useful to both basic and translational GBM research.

SUBMITTER: Xie Y

PROVIDER: S-EPMC4634360 | biostudies-literature | 2015 Oct

REPOSITORIES: biostudies-literature

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The Human Glioblastoma Cell Culture Resource: Validated Cell Models Representing All Molecular Subtypes.

Xie Yuan Y Bergström Tobias T Jiang Yiwen Y Johansson Patrik P Marinescu Voichita Dana VD Lindberg Nanna N Segerman Anna A Wicher Grzegorz G Niklasson Mia M Baskaran Sathishkumar S Sreedharan Smitha S Everlien Isabelle I Kastemar Marianne M Hermansson Annika A Elfineh Lioudmila L Libard Sylwia S Holland Eric Charles EC Hesselager Göran G Alafuzoff Irina I Westermark Bengt B Nelander Sven S Forsberg-Nilsson Karin K Uhrbom Lene L

EBioMedicine 20150815 10

Glioblastoma (GBM) is the most frequent and malignant form of primary brain tumor. GBM is essentially incurable and its resistance to therapy is attributed to a subpopulation of cells called glioma stem cells (GSCs). To meet the present shortage of relevant GBM cell (GC) lines we developed a library of annotated and validated cell lines derived from surgical samples of GBM patients, maintained under conditions to preserve GSC characteristics. This collection, which we call the Human Glioblastoma ...[more]

PMID: 26629530

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Project description:Colorectal cancer (CRC) is a heterogeneous disease. More insight into the biological diversity of CRC is needed to improve therapeutic outcomes. Established CRC cell lines are frequently used and were shown to be representative models of the main subtypes of CRC at the genomic and transcriptomic level. In the present work, we established stable, luciferase expressing derivatives from 10 well-established CRC cell lines, generated spheroids and subcutaneous xenograft tumors in nude mice, and performed comparative characterization of these model systems. Transcriptomic analyses revealed the close relation of cell lines with their derived spheroids and xenograft tumors. The preclinical model systems clustered with patient tumor samples when compared to normal tissue thereby confirming that cell-line-based tumor models retain specific characteristics of primary tumors. Xenografts showed different differentiation patterns and bioluminescence imaging revealed metastatic spread to the lungs. In addition, the models were classified according to the CMS classification system, with further sub-classification according to the recently identified two intrinsic epithelial tumor cell states of CRC, iCMS2 and iCMS3. The combined data showed that regarding primary tumor characteristics, 3D-spheroid cultures resemble xenografts more closely than 2D-cultured cells do. Furthermore, we set up a bioluminescence-based spheroid cytotoxicity assay in order to be able to perform dose-response relationship studies in analogy to typical monolayer assays. Applying the established assay, we studied the efficacy of oxaliplatin. Seven of the ten used cell lines showed a significant reduction in the response to oxaliplatin in the 3D-spheroid model compared to the 2D-monolayer model. Therapy studies in selected xenograft models confirmed the response or lack of response to oxaliplatin treatment. Analyses of differentially expressed genes in these models identified CAV1 as a possible marker of oxaliplatin resistance. In conclusion, we established a combined 2D/3D, in vitro/in vivo model system representing the heterogeneity of CRC, which can be used in preclinical research applications.

Dataset Information

The Human Glioblastoma Cell Culture Resource: Validated Cell Models Representing All Molecular Subtypes.

Publications

The Human Glioblastoma Cell Culture Resource: Validated Cell Models Representing All Molecular Subtypes.

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