Hallmarks of tumor-associated microglia response to experimental U87 human glioblastoma xenograft

Tihomir Dugandžija; Jovana Drljača; Dragica Bulajić; Aleksandra Isaković; Nebojša Stilinović; Slobodan Sekulić; Ivan Čapo

doi:10.1016/j.tice.2021.101557

Hallmarks of tumor-associated microglia response to experimental U87 human glioblastoma xenograft

Tissue Cell. 2021 Oct:72:101557. doi: 10.1016/j.tice.2021.101557. Epub 2021 May 23.

Authors

Tihomir Dugandžija¹, Jovana Drljača², Dragica Bulajić³, Aleksandra Isaković⁴, Nebojša Stilinović⁵, Slobodan Sekulić⁶, Ivan Čapo⁷

Affiliations

¹ Faculty of Medicine, Department of Epidemiology, University of Novi Sad, Hajduk Veljkova 3, Novi Sad, 21000, Serbia; Oncology Institute of Vojvodina, Put doktora Goldmana 4, Sremska Kamenica, 21204, Serbia.
² Faculty of Medicine, University of Novi Sad, Hajduk Veljkova 3, Novi Sad, 21000, Serbia; Center for Medical and Pharmaceutical Investigations and Quality Control, Faculty of Medicine, University of Novi Sad, Hajduk Veljkova 3, Novi Sad, 21000, Serbia. Electronic address: jovana.drljaca@uns.ac.rs.
³ Faculty of Medicine, University of Novi Sad, Hajduk Veljkova 3, Novi Sad, 21000, Serbia; Center for Medical and Pharmaceutical Investigations and Quality Control, Faculty of Medicine, University of Novi Sad, Hajduk Veljkova 3, Novi Sad, 21000, Serbia.
⁴ Institute of Medical and Clinical Biochemistry, School of Medicine, University of Belgrade, Pasterova 2, Belgrade, 11000, Serbia.
⁵ Faculty of Medicine, Department of Pharmacology, Toxicology and Clinical Pharmacology, University of Novi Sad, Hajduk Veljkova 3, Novi Sad, 21000, Serbia.
⁶ Faculty of Medicine, University of Novi Sad, Hajduk Veljkova 3, Novi Sad, 21000, Serbia; Department of Neurology, University Hospital, Clinical Center of Vojvodina, Hajduk Veljkova 1-7, Novi Sad, 21000, Serbia.
⁷ Center for Medical and Pharmaceutical Investigations and Quality Control, Faculty of Medicine, University of Novi Sad, Hajduk Veljkova 3, Novi Sad, 21000, Serbia; Faculty of Medicine, Department of Histology and Embryology, University of Novi Sad, Hajduk Veljkova 3, Novi Sad, 21000, Serbia.

PMID: 34051646
DOI: 10.1016/j.tice.2021.101557

Abstract

Glioblastoma (GBM) is one of the deadliest primary brain neoplasm, heavily infiltrated with tumor-associated microglia/macrophages (TAM), which has received a great deal of interest. Bearing in mind that the number of peripheral macrophages by the 14^th day is negligible, in our study TAM were referred to as microglia. Here we evaluated histopathological characterization of TAM and kinetics of their infiltration in U87 orthotopic GBM, a commonly used model in preclinical research. To mimic different stages of GBM growth, we evaluated three-time points. Our data showed that the highest areal density of TAM was 7 days after GBM inoculation, with ability to proliferate early after initiation of GBM growth. The areal density of TAM within the tumor correlated with GBM growth and proliferation. Moreover, microglia underwent substantial morphological changes upon exposure to GBM cells. A transition from ramified morphology in peritumoral area to ameboid shape with larger soma and shortened, thick branches in the tumor core was observed. Higher areal fraction of blood vessels also correlated with the areal density of TAM. Given these pro-invasive features of microglia, this GBM model represents a good basis for further testing microglia as a target and new strategy to fight with.

Keywords: Experimental animal model; Glioblastoma; Microglia; Tumor microenvironment.

MeSH terms

Animals
Brain Neoplasms / pathology*
Cell Line, Tumor
Disease Models, Animal*
Glioblastoma / pathology*
Heterografts
Humans
Male
Microglia / pathology
Rats
Rats, Wistar
Tumor-Associated Macrophages / pathology*