High levels of WNT-5A in human glioma correlate with increased presence of tumor-associated microglia/monocytes.
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.
Section of Receptor Biology & Signaling, Deptartment Physiology & Pharmacology, Karolinska Institutet, S17177, Stockholm, Sweden.
Jacomijn P
JP
Dijksterhuis
Section of Receptor Biology & Signaling, Deptartment Physiology & Pharmacology, Karolinska Institutet, S17177, Stockholm, Sweden.
Elisa
E
Arthofer
Department of Immunology, Genetics and Pathology (IGP), Science for Life Laboratory, Uppsala University, SE-751 85 Uppsala, Sweden.
Voichita D
VD
Marinescu
Department of Immunology, Genetics and Pathology (IGP), Science for Life Laboratory, Uppsala University, SE-751 85 Uppsala, Sweden.
Sven
S
Nelander
Science for Life Laboratory, KTH-Royal Institute of Technology, SE-171 21 Stockholm, Sweden.
Mathias
M
Uhlén
Department of Immunology, Genetics and Pathology (IGP), Science for Life Laboratory, Uppsala University, SE-751 85 Uppsala, Sweden.
Frederik
F
Pontén
Science for Life Laboratory, Department of Neuroscience, Karolinska Institutet, S-17177 Stockholm, Sweden.
Jan
J
Mulder
Section of Receptor Biology & Signaling, Deptartment Physiology & Pharmacology, Karolinska Institutet, S17177, Stockholm, Sweden; Faculty of Science, Institute of Experimental Biology, Masaryk University, 611 37 Brno, Czech Republic. Electronic address: gunnar.schulte@ki.se.
Gunnar
G
Schulte
D019295:Computational Biology; D005260:Female; D005910:Glioma / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D008297:Male; D017628:Microglia / Q000378:metabolism* / Q000473:pathology; D009000:Monocytes / Q000378:metabolism* / Q000473:pathology; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D046888:Tissue Array Analysis; D051153:Wnt Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D000071818:Wnt-5a Protein
D011518:Proto-Oncogene Proteins; C085389:WNT5A protein, human; D051153:Wnt Proteins; D000071818:Wnt-5a Protein
Glioma; Major histocompatibility complex II; Microglia; Tumor microenvironment; WNT-5A