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Updated: May 15, 2026
Coculture Assays to Study Macrophage and Microglia Stimulation of Glioblastoma Invasion
Published on: October 20, 2016
Characterization of microglia/macrophages in gliomas developed in S-100β-v-erbB transgenic rats
Atsushi Sasaki1, Hideaki Yokoo, Yuko Tanaka
1Department of Pathology, Saitama Medical University, Saitama.
Abstract:
Glioma-infiltrating microglia/macrophages are referred to as tumor-associated macrophages (TAMs). Transgenic (TG) rats expressing v-erbB, which is a viral form of the epidermal growth factor receptor, under transcriptional regulation by the S100-β promoter, develop brain tumors. This study was designed to clarify the pathological characteristics of TAMs in these experimental tumors. We carried out immunohistochemical and morphometrical analyses of microglia/macrophages in brain tumors (5 malignant glioma, 4 anaplastic oligodendroglioma, 4 astrocytoma) that developed in TG rats. TAMs with ionized calcium-binding adaptor molecule 1 (Iba1) positivity and morphology of activated, non-phagocytic microglia increased within and around the tumors in malignant gliomas and anaplastic astrocytomas. The Iba1-positive TAMs of the tumor core were significantly more activated than Iba1-positive microglia of non-neoplastic brain tissue in intraparenchymal anaplastic oligodendrogliomas. Iba1 expression showed a significant positive correlation to Ki-67 expression in all the gliomas. Most TAMs showed no or little expression against CD68, CD163 or CD204, although CD204-positive TAMs were observed in necrosis as well as in the proliferating vascular wall. In conclusion, S-100β-v-erbB TG rats may serve as a useful animal model for further analysis of TAMs in terms of tumor cell proliferation, microvascular proliferation and phagocytosis, and as a tool for therapeutic use in malignant gliomas, although it should be noted that the polarization of TAMs toward the M2 phenotype remains unclear.
Insights
Tumor-associated macrophages (TAMs) in experimental brain tumors of transgenic rats show increased activation, correlating with tumor cell proliferation. These rats offer a model for studying TAMs in glioma, though M2 polarization is unclear.
Area of Science:
- Neuro-oncology
- Immunology
- Pathology
Background:
- Glioma-infiltrating microglia/macrophages are termed tumor-associated macrophages (TAMs).
- Transgenic (TG) rats expressing v-erbB develop brain tumors, providing an experimental model.
- Understanding TAMs' pathological characteristics is crucial for glioma research.
Purpose of the Study:
- To clarify the pathological characteristics of TAMs in experimental brain tumors of S100β-v-erbB TG rats.
- To analyze the activation state and markers of TAMs within these tumors.
- To evaluate the potential of this TG rat model for TAM research.
Main Methods:
- Immunohistochemical and morphometrical analyses of microglia/macrophages (TAMs) in TG rat brain tumors.
- Assessment of ionized calcium-binding adaptor molecule 1 (Iba1) expression and morphology.
- Correlation analysis of Iba1 expression with Ki-67 and other markers (CD68, CD163, CD204).
Main Results:
- Activated, non-phagocytic Iba1-positive TAMs increased within and around tumors, particularly in malignant gliomas and anaplastic astrocytomas.
- TAMs in anaplastic oligodendroglioma cores showed significantly higher activation than normal brain microglia.
- Iba1 expression positively correlated with Ki-67 across all gliomas; CD204 was noted in necrosis and vascular walls.
Conclusions:
- S100β-v-erbB TG rats represent a valuable model for studying TAMs in relation to tumor cell proliferation and microvascular proliferation in malignant gliomas.
- The model aids in analyzing TAM phagocytosis, but M2 phenotype polarization requires further investigation.
- This TG rat model shows promise as a tool for therapeutic strategies in malignant gliomas.
