Characterization of microglia/macrophages in gliomas developed in S‐100β‐v‐erbB transgenic rats. Issue 5 (20th January 2013) - Sasaki, Atsushi
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.