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Astrocytes enhance glioblastoma growth.
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2020 (English)In: Glia, ISSN 0894-1491, E-ISSN 1098-1136, Vol. 68, no 2, p. 316-327Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
2020. Vol. 68, no 2, p. 316-327
Keywords [en]
astrocytes, glioblastoma, glioma, microenvironment, proliferation
National Category
Medical Biotechnology Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Identifiers
URN: urn:nbn:se:uu:diva-399954DOI: 10.1002/glia.23718PubMedID: 31509308OAI: oai:DiVA.org:uu-399954DiVA, id: diva2:1379501
Available from: 2019-12-17 Created: 2019-12-17 Last updated: 2020-02-17Bibliographically approved

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Nelander, SvenKrona, Cecilia

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