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

doi:10.1016/j.isci.2018.10.011

Microglia Induce PDGFRB Expression in Glioma Cells to Enhance Their Migratory Capacity

iScience. 2018 Nov 30:9:71-83. doi: 10.1016/j.isci.2018.10.011. Epub 2018 Oct 16.

Authors

Tatjana Wallmann¹, Xing-Mei Zhang², Majken Wallerius¹, Sara Bolin³, Anne-Laure Joly⁴, Caroline Sobocki¹, Lina Leiss⁵, Yiwen Jiang⁶, Jonas Bergh⁷, Eric C Holland⁸, Per Ø Enger⁹, John Andersson⁴, Fredrik J Swartling³, Hrvoje Miletic¹⁰, Lene Uhrbom³, Robert A Harris², Charlotte Rolny¹¹

Affiliations

¹ Karolinska Institutet, Department of Oncology-Pathology, CCK, R8:01, 171 76 Stockholm, Sweden.
² Karolinska Institutet, Department of Clinical Neuroscience, Karolinska Hospital at Solna, CMM, 171 76 Stockholm, Sweden.
³ Uppsala University, Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Rudbeck Laboratory, 751 85 Uppsala, Sweden.
⁴ Karolinska Institutet, Department of Medicine, CMM, 171 76 Stockholm, Sweden.
⁵ 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.
⁶ 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.
⁷ Karolinska Institutet, Department of Oncology-Pathology, CCK, R8:01, 171 76 Stockholm, Sweden; Radiumhemmet, Karolinska University Hospital, 171 76 Stockholm, Sweden.
⁸ Division of Human Biology, Solid Tumor and Translational Research, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
⁹ Oncomatrix Research Lab, University of Bergen, Bergen, Norway; Department of Neurosurgery, Haukeland University Hospital, Bergen, Norway.
¹⁰ Department of Pathology, Haukeland University Hospital, Bergen, Norway; Department of Biomedicine, University of Bergen, Bergen, Norway.
¹¹ Karolinska Institutet, Department of Oncology-Pathology, CCK, R8:01, 171 76 Stockholm, Sweden. Electronic address: [email protected].

Abstract

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.

Keywords: Cancer; Immunology; Molecular Mechanism of Behavior; Pathophysiology.