Microglia Induce PDGFRB Expression in Glioma Cells to Enhance Their Migratory Capacity
Tatjana Wallmann,
Xing-Mei Zhang,
Majken Wallerius,
Sara Bolin,
Anne-Laure Joly,
Caroline Sobocki,
Lina Leiss,
Yiwen Jiang,
Jonas Bergh,
Eric C. Holland,
Per Ø. Enger,
John Andersson,
Fredrik J. Swartling,
Hrvoje Miletic,
Lene Uhrbom,
Robert A. Harris,
Charlotte Rolny
Affiliations
Tatjana Wallmann
Karolinska Institutet, Department of Oncology-Pathology, CCK, R8:01, 171 76 Stockholm, Sweden
Xing-Mei Zhang
Karolinska Institutet, Department of Clinical Neuroscience, Karolinska Hospital at Solna, CMM, 171 76 Stockholm, Sweden
Majken Wallerius
Karolinska Institutet, Department of Oncology-Pathology, CCK, R8:01, 171 76 Stockholm, Sweden
Sara Bolin
Uppsala University, Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Rudbeck Laboratory, 751 85 Uppsala, Sweden
Anne-Laure Joly
Karolinska Institutet, Department of Medicine, CMM, 171 76 Stockholm, Sweden
Caroline Sobocki
Karolinska Institutet, Department of Oncology-Pathology, CCK, R8:01, 171 76 Stockholm, Sweden
Lina Leiss
Karolinska Institutet, Department of Oncology-Pathology, CCK, R8:01, 171 76 Stockholm, Sweden; Neuro Clinic, Haukeland University Hospital, Bergen, Norway; Oncomatrix Research Lab, University of Bergen, Bergen, Norway
Yiwen Jiang
Uppsala University, Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Rudbeck Laboratory, 751 85 Uppsala, Sweden; Karolinska Institutet, Department of Medical Biochemistry and Biophysics, 17177 Stockholm, Sweden
Jonas Bergh
Karolinska Institutet, Department of Oncology-Pathology, CCK, R8:01, 171 76 Stockholm, Sweden; Radiumhemmet, Karolinska University Hospital, 171 76 Stockholm, Sweden
Eric C. Holland
Division of Human Biology, Solid Tumor and Translational Research, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA
Per Ø. Enger
Oncomatrix Research Lab, University of Bergen, Bergen, Norway; Department of Neurosurgery, Haukeland University Hospital, Bergen, Norway
John Andersson
Karolinska Institutet, Department of Medicine, CMM, 171 76 Stockholm, Sweden
Fredrik J. Swartling
Uppsala University, Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Rudbeck Laboratory, 751 85 Uppsala, Sweden
Hrvoje Miletic
Department of Pathology, Haukeland University Hospital, Bergen, Norway; Department of Biomedicine, University of Bergen, Bergen, Norway
Lene Uhrbom
Uppsala University, Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Rudbeck Laboratory, 751 85 Uppsala, Sweden
Robert A. Harris
Karolinska Institutet, Department of Clinical Neuroscience, Karolinska Hospital at Solna, CMM, 171 76 Stockholm, Sweden
Charlotte Rolny
Karolinska Institutet, Department of Oncology-Pathology, CCK, R8:01, 171 76 Stockholm, Sweden; Corresponding author
Summary: High-grade gliomas (HGGs) are the most aggressive and invasive primary brain tumors. The platelet-derived growth factor (PDGF) signaling pathway drives HGG progression, and enhanced expression of PDGF receptors (PDGFRs) is a well-established aberration in a subset of glioblastomas (GBMs). PDGFRA is expressed in glioma cells, whereas PDGFRB is mostly restricted to the glioma-associated stroma. Here we show that the spatial location of TAMMs correlates with the expansion of a subset of tumor cells that have acquired expression of PDGFRB in both mouse and human low-grade glioma and HCGs. Furthermore, M2-polarized microglia but not bone marrow (BM)-derived macrophages (BMDMs) induced PDGFRB expression in glioma cells and stimulated their migratory capacity. These findings illustrate a heterotypic cross-talk between microglia and glioma cells that may enhance the migratory and invasive capacity of the latter by inducing PDGFRB. : Pathophysiology; Molecular Mechanism of Behavior; Immunology; Cancer Subject Areas: Pathophysiology, Molecular Mechanism of Behavior, Immunology, Cancer
