講演情報
[O17-1]M2マクロファージにおける低酸素環境によるTGF-α, βの発現制御
○寺本 晃治1,2, 住本 秀敏1,2, 醍醐 弥太郎1,2,3 (1.滋賀医科大学 医学部 臨床腫瘍学講座（腫瘍内科）, 2.滋賀医科大学 先端がん研究センター, 3.東京大学医科学研究所、抗体・ワクチンセンター)
Background: Tumor-associated macrophages (TAM) possess a phenotype of M2 macrophages and contribute to generation of pro-tumor microenvironment in cancer. In order to elucidate the roles of TAM in tumor growth, we focused on transforming growth factor-alpha (TGF-α) and -beta (TGF-β) which are released by TAM and activate their downstream signaling pathway for cell growth. We also focused on hypoxia which is a physiological feature of tumor microenvironment, and examined the regulatory mechanism of these cytokines by hypoxia in M2 macrophages. Methods: M2 macrophages were generated from peripheral monocytes and were exposed to deferoxamine mesylate (DFO), an inhibitor of hypoxia-inducible factor 1α (HIF1α) degradation for 5 hours. mRNAs were extracted from these cells, and the levels of TGF-α and TGF-β mRNAs were measured by real time-qPCR. Results: M2 macrophages generated in vitro were positive for CD206 and negative for CD163. The levels of TGF-α as well as TGF-β mRNA were upregulated after HIF1α accumulation. In these cells, median RQ was 2.4 and 1.9 in TGF-α and TGF-β mRNA expression, respectively. Discussion: The data suggest that TGF-α and TGF-β expression might be upregulated by hypoxic tumor microenvironment. Although further validation is necessary, upregulation of these cytokines levels by TAM might contribute to tumor cell growth.