title: Characterization of microglia/macrophages in gliomas developed in S-100β-v-erbB transgenic rats.
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.
authors: Department of Pathology, Saitama Medical University, Saitama.
authors: Atsushi
authors: A
authors: Sasaki
authors: Hideaki
authors: H
authors: Yokoo
authors: Yuko
authors: Y
authors: Tanaka
authors: Taku
authors: T
authors: Homma
authors: Yoichi
authors: Y
authors: Nakazato
authors: Hiroko
authors: H
authors: Ohgaki
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000276:immunology* / Q000473:pathology; D005910:Glioma / Q000276:immunology* / Q000473:pathology; D008264:Macrophages / Q000276:immunology* / Q000473:pathology; D017628:Microglia / Q000276:immunology* / Q000473:pathology; D009361:Neoplasm Invasiveness; D051381:Rats; D055647:Rats, Transgenic
keywords: glioma; microglia; transgenic rats; tumor-associated macrophages; v-erbB