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High levels of WNT-5A in human glioma correlate with increased presence of tumor-associated microglia/monocytes
Karolinska Inst, Sect Receptor Biol & Signaling, Deptartment Physiol & Pharmacol, S-17177 Stockholm, Sweden..
Karolinska Inst, Sect Receptor Biol & Signaling, Deptartment Physiol & Pharmacol, S-17177 Stockholm, Sweden..
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Neuro-Oncology. Uppsala University, Science for Life Laboratory, SciLifeLab.
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2015 (English)In: Experimental Cell Research, ISSN 0014-4827, E-ISSN 1090-2422, Vol. 339, no 2, 280-288 p.Article in journal (Refereed) Published
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Abstract [en]

Malignant gliomas are among the most severe types of cancer, and the most common primary brain tumors. Treatment options are limited and the prognosis is poor. WNT-5A, a member of the WNT family of lipoglycoproteins, plays a role in oncogenesis and tumor progression in various cancers, whereas the role of WNT-5A in glioma remains obscure. Based on the role of WNT-5A as an oncogene, its potential to regulate microglia cells and the glioma-promoting capacities of microglia cells, we hypothesize that WNT-5A has a role in regulation of immune functions in glioma. We investigated WNT-5A expression by in silico analysis of the cancer genome atlas (TCGA) transcript profiling of human glioblastoma samples and immunohistochemistry experiments of human glioma tissue microarrays (TMA). Our results reveal higher WNT-5A protein levels and mRNA expression in a subgroup of gliomas (WNT-5A(high)) compared to non-malignant control brain tissue. Furthermore, we show a significant correlation between WNT-5A in the tumor and presence of major histocompatibility complex Class II-positive microglia/monocytes. Our data pinpoint a positive correlation between WNT-5A and a proinflammatory signature in glioma. We identify increased presence of microglia/monocytes as an important aspect in the inflammatory transformation suggesting a novel role for WNT-5A in human glioma.

Place, publisher, year, edition, pages
2015. Vol. 339, no 2, 280-288 p.
Keyword [en]
WNT-5A, Microglia, Glioma, Major histocompatibility complex II, Tumor microenvironment
National Category
Cell and Molecular Biology
Identifiers
URN: urn:nbn:se:uu:diva-274284DOI: 10.1016/j.yexcr.2015.10.022ISI: 000366618700012OAI: oai:DiVA.org:uu-274284DiVA: diva2:898578
Funder
Swedish Research Council, K2008-68P-20810-01-4 K2008-333 68X-20805-01-4 K2012-67X-20805-05-3Swedish Cancer Society, CAN 2008/539 2011/690 CAN 2014/659Swedish Childhood Cancer Foundation, PROJ11/057Knut and Alice Wallenberg Foundation, KAW2008.0149
Available from: 2016-01-28 Created: 2016-01-20 Last updated: 2017-11-30Bibliographically approved

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Marinescu, Voichita D.Nelander, SvenPonten, Frederik

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Department of Medical Biochemistry and MicrobiologyScience for Life Laboratory, SciLifeLabNeuro-OncologyDepartment of Immunology, Genetics and Pathology
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Experimental Cell Research
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