Astrocytes enhance glioblastoma growth.


Journal

Glia
ISSN: 1098-1136
Titre abrégé: Glia
Pays: United States
ID NLM: 8806785

Informations de publication

Date de publication:
02 2020
Historique:
received: 06 03 2019
revised: 24 08 2019
accepted: 26 08 2019
pubmed: 12 9 2019
medline: 24 6 2020
entrez: 12 9 2019
Statut: ppublish

Résumé

Glioblastoma (GBM) is a deadly disease with a need for deeper understanding and new therapeutic approaches. The microenvironment of glioblastoma has previously been shown to guide glioblastoma progression. In this study, astrocytes were investigated with regard to their effect on glioblastoma proliferation through correlative analyses of clinical samples and experimental in vitro and in vivo studies. Co-culture techniques were used to investigate the GBM growth enhancing potential of astrocytes. Cell sorting and RNA sequencing were used to generate a GBM-associated astrocyte signature and to investigate astrocyte-induced GBM genes. A NOD scid GBM mouse model was used for in vivo studies. A gene signature reflecting GBM-activated astrocytes was associated with poor prognosis in the TCGA GBM dataset. Two genes, periostin and serglycin, induced in GBM cells upon exposure to astrocytes were expressed at higher levels in cases with high "astrocyte signature score". Astrocytes were shown to enhance glioblastoma cell growth in cell lines and in a patient-derived culture, in a manner dependent on cell-cell contact and involving increased cell proliferation. Furthermore, co-injection of astrocytes with glioblastoma cells reduced survival in an orthotopic GBM model in NOD scid mice. In conclusion, this study suggests that astrocytes contribute to glioblastoma growth and implies this crosstalk as a candidate target for novel therapies.

Identifiants

pubmed: 31509308
doi: 10.1002/glia.23718
doi:

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

316-327

Informations de copyright

© 2019 Wiley Periodicals, Inc.

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Auteurs

Alessandro Mega (A)

Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.

Mette Hartmark Nilsen (M)

Department of Biomedicine, University of Bergen, Bergen, Norway.

Lina Wik Leiss (LW)

Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.

Nicholas P Tobin (NP)

Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.

Hrvoje Miletic (H)

Department of Biomedicine, University of Bergen, Bergen, Norway.
Department of Pathology, Haukeland University Hospital, Bergen, Norway.

Linda Sleire (L)

Department of Biomedicine, University of Bergen, Bergen, Norway.
Department of Neurology, Haukeland University Hospital, Bergen, Norway.

Carina Strell (C)

Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.

Sven Nelander (S)

Department of Immunology, Genetics and Pathology, Neuro-Oncology, Uppsala University, Uppsala, Sweden.

Cecilia Krona (C)

Department of Immunology, Genetics and Pathology, Neuro-Oncology, Uppsala University, Uppsala, Sweden.

Daniel Hägerstrand (D)

Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.

Per Ø Enger (PØ)

Department of Biomedicine, University of Bergen, Bergen, Norway.

Monica Nistér (M)

Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.

Arne Östman (A)

Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.

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