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.
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.
Tissue Cell. 2021 Oct;72:101557. doi: 10.1016/j.tice.2021.101557. Epub 2021 May 23.
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 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.
胶质母细胞瘤（GBM）是最致命的原发性脑肿瘤之一，大量浸润着肿瘤相关的小胶质细胞/巨噬细胞（TAM），这引起了广泛的关注。考虑到第 14 天时外周巨噬细胞的数量可以忽略不计，在我们的研究中，TAM 被称为小胶质细胞。在这里，我们评估了 U87 原位 GBM 中 TAM 的组织病理学特征及其浸润动力学，U87 原位 GBM 是临床前研究中常用的模型。为了模拟 GBM 生长的不同阶段，我们评估了三个时间点。我们的数据表明，TAM 的最高面积密度出现在 GBM 接种后 7 天，并且在 GBM 生长开始后能够早期增殖。TAM 的面积密度与 GBM 的生长和增殖相关。此外，小胶质细胞在暴露于 GBM 细胞后发生了显著的形态变化。在肿瘤周围区域，从有分支的形态转变为阿米巴样形态，胞体较大，分支缩短且变粗，在肿瘤核心中观察到这种形态变化。较高的血管面积分数也与 TAM 的面积密度相关。鉴于小胶质细胞的这些侵袭前特征，该 GBM 模型为进一步将小胶质细胞作为靶点以及打击 GBM 的新策略提供了良好的基础。
