Hallmarks of tumor-associated microglia response to experimental U87 human glioblastoma xenograft. (October 2021)

• Record Type: Journal Article
• Authors: Dugandžija, Tihomir; Drljača, Jovana; Bulajić, Dragica; Isaković, Aleksandra; Stilinović, Nebojša; Sekulić, Slobodan; Čapo, Ivan
• Is Part Of: Tissue & cell. Volume 72(2021)
• Publication Date: 2021-10
• Subjects: GBM glioblastoma -- TAM tumor-associated microglia/macrophages -- PBS phosphate buffer saline; Microglia -- Glioblastoma -- Tumor microenvironment -- Experimental animal model; Cytology -- Periodicals; 571.5
• DOI: 10.1016/j.tice.2021.101557
• Languages: English
• ISSNs: 0040-8166

Abstract

Graphical abstract: Highlights: Microglia in U87 GBM xenograft showed similar pattern as in human glioblastomas. Microglia infiltration closely correlated with tumor volume, proliferation and vessel density in U87 GBM xenograft. This U87 GBM xenograft represents a good model for further testing microglia as a target and new strategy to fight with. 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.